research of rabbits

Rabbits: Habits, diet & other facts

Rabbits are social animals, with colonies of the fluffy mammal occupying most of the world’s land masses.

• Reproduction

Classification/ taxonomy

Conservation status, other facts, additional resources, bibliography.

Rabbits are small mammals with fluffy, short tails, whiskers and distinctive long ears. There 29 species around the world, according to Nature by PBS and, while they live in many different environments, they have many things in common.

Rabbits and hares are in the same taxonomic family, Leporidae, but they are in different genera. There are 11 genera within the family, but the term “true hares” refers only to species in the genus Lepus ; all others are rabbits. Also, the American Rabbit Breeders Association (ARBA) recognizes 49 rabbit breeds.

How big are rabbits?

Some rabbits are about the size of a cat, and some can grow to be as big as a small child. Small rabbits, such as pygmy rabbits, can be as little as 9.3 inches (24 centimeters) in length and weigh less than a pound, according to the U.S. Fish and Wildlife Service . Larger species grow to 20 inches (50 cm) and more than 10 lbs. (4.5 kilograms). 

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According to the Journal of Applied Animal Research , the Flemish Giant is the largest rabbit breed in the world. The average weight of the Flemish Giant is 25 lbs (11 kg), according to World Atlas . Other large rabbit species include the Continental Giant at 16 lbs (7 kg) and the Blanc De Bouscat at 15 lbs (6 kg).   . The world's longest individual rabbit, according to Guinness World Records , is a Flemish giant that clocked in at 4 feet 3 inches (129 cm) and 49 pounds (22 kg).

Small rabbit breeds include the Britannia Petite, under 2.5 lbs. (1.1 kg); Netherland dwarf, under 2.5 lbs.; dwarf hotot, under 3 lbs. (1.3 kg); and Himalayan, 2.5 to 4.5 lbs. (1.1 to 2 kg).

Rabbit reproduction

Rabbits are known for their insatiable reproductive habits for good reason. They breed three to four times each year. This is because only 15 percent of baby rabbits make it to their first birthday, according to the Animal Diversity Web (ADW) . So, to ensure that the population grows, rabbits have more babies. 

According to the Wildlife Center of Virginia , in each pregnancy a female rabbit produces between one and twelve babies, called kittens or kits. However, the average number is five. 

After around three  weeks, a kit can care for itself, according to the Wildlife Center of Virginia. In two or three months it is ready to start a family of its own. If there is a lack of natural predators, an area can quickly become overrun with rabbits.

What do rabbits eat?

Rabbits are herbivores , according to the Journal of Mammalogy . This means that they have a plant-based diet and do not eat meat. Their diets include grasses, clover and some cruciferous plants, such as broccoli and Brussels sprouts. They are opportunistic feeders, according to the University of Missouri , and so also eat fruits , seeds, roots, buds, and tree bark.

Where do they live?

While originally from Europe and Africa, rabbits are now found all over the world. Wild rabbits occupy most of the world’s continents, except for Asia and Antarctica, according to ADW . Although originally absent from many countries, such as Australia and New Zealand, rabbits have been introduced to these locations during the last few centuries, according to the journal Mammal Review .

Domestic rabbits need a regulated environment to protect against heat exhaustion or hypothermia. Wild rabbits don't have this problem and make their homes in various temperature extremes. Wild rabbits can be found in woods, forests, meadows, grasslands, deserts, tundra and wetlands. 

Wild rabbits create their own homes by tunneling into the ground. These tunnel systems are called warrens and include rooms for nesting and sleeping. They also have multiple entrances for quick escape. Warrens can be as deep as 9.84 feet (3 meters) underground, according to the Textbook of Rabbit Medicine .

Rabbits’ habits

Rabbits are very social creatures and live in large groups called colonies. The busiest time of day for rabbits is at dusk and dawn, according to the Proceedings of the 8th World Rabbit Congress . This is when they venture out to find food. The low light allows them to hide from predators. 

Predators — which include owls, hawks, eagles, falcons, wild dogs , feral cats and ground squirrels — are a constant threat. The rabbit’s long legs and ability to run for long periods at high speeds are likely evolutionary adaptations to help them elude things that want to eat them.

This is the taxonomy of rabbits, according to ADW, the International Union for Conservation of Nature (IUCN) and the Integrated Taxonomic Information System (ITIS):

Kingdom : Animalia 

Phylum : Chordata 

Subphylum : Vertebrata 

Class : Mammalia 

Order : Lagomorpha 

Family : Leporidae 

Genera : 

• Brachylagus  (pygmy rabbits)
• Bunolagus  (riverine rabbits)
• Nesolagus  (Sumatran rabbits, Annamite striped rabbits)
• Oryctolagus  (Old World rabbits, European rabbits, domestic rabbits)
• Pentalagus  (Amami rabbits)
• Poelagus  (Bunyoro rabbits)
• Romerolagus  (volcano rabbits)
• Sylvilagus  (cottontail rabbits)

Species : There are more than 50 species of rabbits. The domestic rabbit is  Oryctolagus cuniculus.

The domestic or European rabbit is considered within near threatened range by the IUCN . Found all over the world, scientists think most populations are descendants of domestic rabbits that were released in the wild. According to the Encyclopedia of Immunobiology , it is native to the Iberian Peninsula, and in that area, populations have declined as much as 95 percent from its 1950 numbers, and about 80 percent of its 1975 numbers. The decline is attributed to habitat loss, disease and hunting. Rabbits are considered pests by many gardeners.

Bunolagus monticularis , the riverine rabbit of South Africa, is critically endangered, according to the IUCN . Of 10 subpopulations, none is estimated to have more than 50 individuals, according to the IUCN’s Red List of Threatened Species. Loss of habitat is the main threat.

Nesolagus netscheri , the Sumatran striped rabbit, is listed by the IUCN as vulnerable. It is a rare species, according to IUCN, and not well known locally. The species lives only on the island of Sumatra, Indonesia, at altitudes between 600 and 1,600 m (1,969 and 5,249 feet).

Pentalagus furnessi (Amami rabbit), which is found only on two Japanese islands, is endangered, according to the IUCN . Populations are declining because of invasive predators and habitat loss caused by forest clearing and resort construction. There are only about 5,000 individuals alive on Amami Island and 400 on Tokuno Island.

Romerolagus diazi (Volcano rabbit) is listed as endangered. It is found only in Mexico near the volcanoes Popocatepetl, Iztaccihuatl, El Pelado and Tlaloc. A 1994 study in the Journal of Mammalogy found between 2,478 and 12,120 individuals, but the population trend is increasing.

Several species of cottontail rabbits (genus Silvilagus ) are listed as near threatened, threatened, vulnerable, endangered and critically endangered. The San José brush rabbit ( Silvilagus mansuetus ) is found only on San José Island in the Gulf of California. The one population occupies an area of about 20 square kilometers (7.7 square miles). Fewer individuals were observed in 2008 compared to studies in 1995 and 1996, although quantities were recorded.

Rabbits can be very crafty and quick. To get away from a predator, a cottontail rabbit will run in a zigzag pattern and reach speeds of up to 18 mph (29 km/h), according to Warnell School of Forestry and Natural Resources at the University of Georgia . 

Their ears can grow to 4 inches (10 cm), according to PDSA . This stretched-out length allows them to better hear predators that may be approaching. It also allows them to stay cool in hot climates. Extra body heat is released through blood vessels in the ear, according to the Biomimicry Institute .

Their eyes are made for safety, too, since each eye can rotate almost 360 degrees, according to North American Nature . This allows them to look behind them without turning their heads.

Rabbits don't get a lot of nourishment from their diet. They often eat their own excrement to access any remaining nourishment that their digestive system may have missed the first time, according to the book Nutrition of the Rabbit .

To read more about why rabbits were introduced to Australia, go to the National Museum Australia website . You can explore the large variety of rabbit breeds at the American Rabbit Breeders Association website.

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"Palatability of plants to small mammals in nonnative grasslands of east-central Illinois". Journal of Mammalogy (2013). https://academic.oup.com/jmammal/article/94/2/427/911348?login=true

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https://mospace.umsystem.edu/xmlui/handle/10355/43374?show=full

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"Textbook of Rabbit Medicine". Molly Varga Smith. Elsevier Health Sciences (2013). https://books.google.co.uk/books

"Sociometric Investigations in Groups of Wild and Domestic Rabbits With One Buck and Two or Three Does". Proceedings- 8th World Rabbit Congress (2004).   http://world-rabbit-science.com/WRSA-Proceedings/Congress-2004-Puebla/Papers/Welfare%20&%20Ethology/W-Hoy.pdf

"Development and Phylogeny of the Immune System". Encylopedia of Immunology (2016).   https://www.sciencedirect.com/topics/neuroscience/myxomatosis

"Distribution and Population Size of Romerolagus diazi on El Pelado Volcano, Mexico". Journal of Mammalogy (1994).   https://www.jstor.org/stable/1382525

"Feeding behaviour of rabbits". Nutrition of the Rabbit (2020).   https://hal.inrae.fr/hal-02569326

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• Published: 15 June 2023

An atlas of rabbit development as a model for single-cell comparative genomics

• Mai-Linh Nu Ton   ORCID: orcid.org/0000-0001-6965-0528 1 , 2   na1 ,
• Daniel Keitley 3   na1 ,
• Bart Theeuwes 1 , 2 ,
• Carolina Guibentif   ORCID: orcid.org/0000-0003-1056-9922 4 ,
• Jonas Ahnfelt-Rønne 5 ,
• Thomas Kjærgaard Andreassen 5 ,
• Fernando J. Calero-Nieto   ORCID: orcid.org/0000-0003-3358-8253 1 , 2 ,
• Ivan Imaz-Rosshandler 1 , 6 ,
• Blanca Pijuan-Sala 7 ,
• Jennifer Nichols 8 ,
• Èlia Benito-Gutiérrez   ORCID: orcid.org/0000-0003-2435-0948 3 ,
• John C. Marioni   ORCID: orcid.org/0000-0001-9092-0852 9 , 10 , 11 &
• Berthold Göttgens   ORCID: orcid.org/0000-0001-6302-5705 1 , 2  

Nature Cell Biology volume  25 ,  pages 1061–1072 ( 2023 ) Cite this article

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• Embryogenesis
• Gene regulatory networks

Traditionally, the mouse has been the favoured vertebrate model for biomedical research, due to its experimental and genetic tractability. However, non-rodent embryological studies highlight that many aspects of early mouse development, such as its egg-cylinder gastrulation and method of implantation, diverge from other mammals, thus complicating inferences about human development. Like the human embryo, rabbits develop as a flat-bilaminar disc. Here we constructed a morphological and molecular atlas of rabbit development. We report transcriptional and chromatin accessibility profiles for over 180,000 single cells and high-resolution histology sections from embryos spanning gastrulation, implantation, amniogenesis and early organogenesis. Using a neighbourhood comparison pipeline, we compare the transcriptional landscape of rabbit and mouse at the scale of the entire organism. We characterize the gene regulatory programmes underlying trophoblast differentiation and identify signalling interactions involving the yolk sac mesothelium during haematopoiesis. We demonstrate how the combination of both rabbit and mouse atlases can be leveraged to extract new biological insights from sparse macaque and human data. The datasets and computational pipelines reported here set a framework for a broader cross-species approach to decipher early mammalian development, and are readily adaptable to deploy single-cell comparative genomics more broadly across biomedical research.

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A single-cell time-lapse of mouse prenatal development from gastrula to birth

Chengxiang Qiu, Beth K. Martin, … Jay Shendure

The changing mouse embryo transcriptome at whole tissue and single-cell resolution

Peng He, Brian A. Williams, … Barbara J. Wold

Primate gastrulation and early organogenesis at single-cell resolution

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Data availability

Raw sequencing data are available through ArrayExpress with the following accessions: scRNA-seq: E-MTAB-11836 ; scATAC-seq: E-MTAB-11804 . Raw histology and RNAscope imaging files are available through the EBI BioImage archive under accession S-BIAD604 . All other links to the data are available at https://marionilab.github.io/RabbitGastrulation2022/ . This includes links to processed single-cell transcriptomics and ATAC-seq data in a variety of formats for loading into both R and Python analysis pipelines. The transcriptomics and imaging data are also available to explore interactively via a web app accessible through the same link. Low-resolution thumbnail images for all generated imaging datasets are additionally provided. Source data are provided with this paper. All other data supporting the findings of this study are available from the corresponding author on reasonable request.

Code availability

Codes are available at https://github.com/MarioniLab/RabbitGastrulation2022 and https://marionilab.github.io/RabbitGastrulation2022/ .

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Acknowledgements

We thank K. Katarzyna and the CRUK CI Genomics Core for their help with the 10x Genomics sample processing; R. Argelaguet for bioinformatic support; N. Wilson for assistance with the facilities and technical support; M. Rostovskaya for discussions around eutherian amnion; M. Keller (Gehlenborg lab) for help in setting up the Vitessce visualization platform. We also thank H. D. Farizi and S. D. Høiberg (Novo Nordisk) for help with rabbit embryo sectioning. M.-L.N.T. is funded by a Herchel Smith PhD Fellowship in Science. D.K. is funded by the Wellcome Mathematical Genomics and Medicine Programme at the University of Cambridge (PFZH/158 RG92770). C.G. was funded by the Swedish Research Council (2017-06278) and by a Swedish Childhood Cancer Fund position grant (TJ2021-0009). I.I.-R. was funded by the Wellcome Mathematical Genomics and Medicine Programme at the University of Cambridge (203942/Z/16/Z; RDAG/426RG86191). Work in the Gottgens group is supported by Wellcome, Bloodwise, MRC and CRUK, and by core support grants from Wellcome to the Wellcome-MRC Cambridge Stem Cell Institute. Work in the Marioni group is supported by core funding from CRUK (C9545/A29580) and by the European Molecular Biology Laboratory. Work in the È.B.-G. lab is supported by CRUK (C9545/A29580). This work was funded as part of a Wellcome grant (220379/B/20/Z) awarded to B.G., J.N. and J.C.M. and the WSSS Dev Ext Wellcome Grant (220152_C_20_Z) awarded to B.G. and J.C.M.

Author information

These authors contributed equally: Mai-Linh N. Ton, Daniel Keitley.

Authors and Affiliations

Department of Haematology, University of Cambridge, Cambridge, UK

Mai-Linh Nu Ton, Bart Theeuwes, Fernando J. Calero-Nieto, Ivan Imaz-Rosshandler & Berthold Göttgens

Wellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK

Mai-Linh Nu Ton, Bart Theeuwes, Fernando J. Calero-Nieto & Berthold Göttgens

Department of Zoology, University of Cambridge, Cambridge, UK

Daniel Keitley & Èlia Benito-Gutiérrez

Inst. Biomedicine, Dept. Microbiology and Immunology, Sahlgrenska Center for Cancer Research, University of Gothenburg, Gothenburg, Sweden

Carolina Guibentif

Global Discovery & Development Sciences, Novo Nordisk A/S, Måløv, Denmark

Jonas Ahnfelt-Rønne & Thomas Kjærgaard Andreassen

Medical Research Council Laboratory of Molecular Biology, Cambridge, UK

Ivan Imaz-Rosshandler

Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany

Blanca Pijuan-Sala

MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK

Jennifer Nichols

Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK

John C. Marioni

European Molecular Biology Laboratory, European Bioinformatics Institute, Cambridge, UK

Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK

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Contributions

C.G., M.-L.N.T. and J.N. performed embryo dissections and generated the scRNA-seq atlas dataset. M.-L.N.T. and F.J.C.-N. generated the scATAC-seq atlas dataset. J.A.-R. And T.K.A. supplied the animals for the experiments and conducted histology and imaging of the embryos. M.-L.N.T. performed pre-processing and initial low-level analysis for both atlases. D.K. performed batch correction and global visualization of the scRNA-seq dataset. D.K. performed cross-species comparisons between the rabbit mouse, macaque and human datasets. D.K. implemented the website. B.T. performed analysis on the scATAC-seq dataset. D.K., M.-L.N.T., B.P.-S., C.G., B.T. and I.I.-R. annotated atlas cell types. M.-L.N.T., B.T. and D.K. analysed the atlas trophoblast cells. J.N., È.B.-G., J.C.M. and B.G. supervised the study. M.-L.N.T., D.K., B.T., B.G., J.C.M. and È.B.-G. wrote the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Èlia Benito-Gutiérrez , John C. Marioni or Berthold Göttgens .

Ethics declarations

Competing interests.

Provision of time-mated rabbit embryos by Labcorp Early Development Laboratories Limited as well as scRNA-seq costs were supported by a research contract agreement with J.A.-R. and T.K.A. at Novo Nordisk A/S. È.B.-G. and J.C.M. have been employees of Genentech since September 2022.

Peer review

Peer review information.

Nature Cell Biology thanks Janet Rossant and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Peer reviewer reports are available.

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Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Extended data

Extended data fig. 1 histology and dissection images reveals early dynamics of early germ layers of rabbit flat-disk embryo..

a) Representative RNAscope image of GD7 rabbit sagittal in utero section showing beginning of gastrulation. TFAP2C and OCT4 mark trophoblast and epiblast-derived cell types, respectively. Arrowheads indicate implantation on the anti-mesometrial side of the embryo. b ) Representative RNAscope image of GD8 rabbit sagittal in utero sections showing germ layer differentiation. (i) Arrowheads indicate implantation sides in the mesometrial direction. TFAP2C marks trophoblast and trophoblast progenitors. (ii) Chorioamnion fold formation can be seen alongside early germ layer differentiation. Chorion consists of a mesoderm inner layer, and amnion has an mesoderm outer layer as captured in the RNAscope image. c ) Representative histology images of rabbit cross-sections in utero and magnification of the embryo to show details and orientation of the embryo in the uterus. cm, cranial mesoderm. d ) Summary of over 650 + H&E and RNAscope images of rabbit sections generated in this study of which the representative images are pulled from. e ) RNAscope image of the vitelline artery (VA) and dorsal aorta (DA) region showing the RUNX1 + CDH5+ presumptive haemogenic endothelium in the ventral portion of the dorsal aorta. f) Representative images of the rabbit embryos and their extraembryonic tissues utilized in this study g ) 13 somite and 16 somite GD9 rabbit embryos microdissected into anterior, mid, and posterior regions for scRNA-seq.

Extended Data Fig. 2 Updated transcriptome annotation improves the quality of processed scRNA-seq data.

a , The distances of intergenic reads to their nearest annotated gene in a single GD8 sample. i ) The distances for a subset of intergenic reads aligned to a region of chromosome 1 are shown. The vertical line indicates the 600 bp extension added to the 3′ ends (see Methods). ii ) Distances are also shown for intergenic reads whose closest annotated gene is GATA1 and SOX9 . b ) The read coverage for the same GD8 sample shows that many reads associated with FOXA2 transcripts are positioned off the 3′ end of the OryCun 2.0 reference annotation. These missing reads are captured by our 600 bp extension. c ) The 3′ extended gene annotations substantially improve the signal obtained after processing with Cell Ranger. d ) Examples of new annotations added from aligning human gene annotations with the rabbit transcriptome. These new annotations overlap positions with high read coverage. e ) The signal captured as a result of the new human gene annotations are consistent with the known expression patterns of SIX3 (forebrain marker) and FOXC1 (mesodermal marker). Intergenic read distances and normalised expression values are available in the source data.

Source data

Extended data fig. 3 rna-seq quality controls..

a ) Number of high-quality cells sampled from each of the 26 scRNA-seq samples. Annotations refer to the anatomical dissections performed for GD9 samples. b ) Distribution of UMIs ( c ) genes detected and ( d ) percentage of mitochondrial reads recorded across cells sampled from each of the 26 scRNA-seq samples (N = 19 embryos), coloured by developmental stage. The lower and upper hinges of the boxplots relate to the first and third quartiles respectively. The center line denotes the median and the whiskers extend to the largest/smallest value no further than 1.5 times the inter-quartile range from the upper/lower hinge respectively. Outlier points are plotted if they exceed the ranges defined by the the upper and lower whiskers. The number of cells used to calculate each statistic are shown in A) and are provided in the source data. e ) Cells from samples taken at each developmental stage and anatomical dissection are highlighted in the UMAP embedding. Following batch correction, the samples are well mixed within the UMAP visualization. A - anterior section, M - mid section; P - posterior section; YS -yolk-sac/extraembryonic tissues; EP - embryo proper. QC values for each cell are available in the source data.

Extended Data Fig. 4 Automated cell type annotation.

a , SingleR predicted cell type annotations for each cell of the rabbit atlas (n = 146,133 cells), following training on the mouse atlas. Only a subset of predicted labels are annotated for visual clarity. Predicted labels for all cells are more easily visualized via the interactive web app, accessible at https://marionilab.github.io/RabbitGastrulation2022/ . b ) Normalised SingleR correlation scores for each rabbit cell against all possible mouse labels. Cells are ordered according to the label assigned by SingleR. The final annotated cell types are also displayed to show how the model predictions relate with those assigned after validation. c ) Cells of the rabbit (top) and mouse (bottom) (Imaz-Rosshandler et al. 23 ) datasets in a SAMap integrated UMAP embedding (n = 576,472 cells). Cells are coloured and annotated according to the cell type labels of each respective atlas. The rabbit (r) and mouse (m) label numberings refer to those in the legends of Fig. 2c and Extended Data Fig. 4a respectively. The full list of IDs can also be found in Supplementary Tables 3–7. Shortened labels for the rabbit extra-embryonic ectoderm cell types have also been added. rT = Trophoblast; rA1 = Amnion 1; rA2 = Amnion 2; rA3 = Amnion 3; rCY = Cytotrophoblast; rSP = SCT progenitors; rES = Early SCT. All panels depict rabbit cells integrated across all samples (N = 19 embryos). SingleR correlation scores and cell type predictions are provided in the source data, along with the integrated UMAP coordinates and final cell type annotations.

Extended Data Fig. 5 Cell type validation.

a ) Cell type proportions across each scRNA-seq sample (N = 19 embryos). Cell types labels are organised based on the stage and dissection they are most abundant. Cell types with low abundance are not shown to preserve visual clairity. b ) Row-normalised gene expression plot showing genes differentially expressed within each cell type. c ) RNAscope images of SERPINC1 and DKK1 helped identify cells of the parietal endoderm (PE). Scale bars = 500 μm. d ) Row-normalised gene expression plot of marker genes used to annotate rabbit extra-embryonic ectoderm cell types. e ) Histology and RNAscope images of a synctial trophoblastic knob expressing TFAP2C at gestational day 8. Scale bar = 100μm. Normalised expression values and cell type annotations (across cells/samples) are available in the Source Data.

Extended Data Fig. 6 Whole embryo scATAC-seq and trophoblast annotation.

a) An illustration of the 8 samples (N = 4 embryos) processed for single-cell ATAC-sequencing. b) Quality control of whole embryo scATAC-seq nuclei based on transcription start site (TSS) enrichment score, total number of fragments per cell, and fraction of reads in peaks (FRIP) across samples. The lower and upper hinges of the boxplots relate to the first and third quartiles respectively. The center line denotes the median and the whiskers extend to the largest/smallest value no further than 1.5 times the inter-quartile range from the upper/lower hinge respectively. Number of nuclei per sample - BGRGP1:26250; BGRGP2 12246; BGRGP3 13008; BGRGP4 4887; BGRGP5 12192; BGRGP6 11982; BGRGP7 11313; BGRGP8 10368. c) The fragment size distribution plotted for each scATAC-seq sample. d) UMAP of 34,082 nuclei that passed quality control for scATAC-seq, colored by predicted cell type inferred from label transfer (see Methods). Inset shows the UMAP colored by developmental stage. e) Linear regression between mean RNA expression and mean ATAC gene scores across cell-types, for top 50 marker genes of annotated cell-types. Top left panel shows linear regression along with values across cell-types for SCT marker genes, other panels only show the linear model itself. Red dotted lines indicate a slope of 1 (see Methods). f) Gene Activity scores of marker genes for refined trophoblast to SCT cell-type annotation. g) Motif enrichment in marker peaks for refined trophoblast to SCT cell-type annotation. h) Genome browser views of the regions surrounding EOMES, CDH5, FOXA2, GATA1 & HDAC6, HBG1/2, PAX6, TBX6 for selected cell-types. N = 4 embryos in all panels. QC values, fragment size distributions, UMAP coordinates, predicted annotations, linear model parameters and heatmap values are all available in the source data.

Extended Data Fig. 7 Rabbit-mouse neighborhood comparisons.

a) Distribution of the number of cells within neighbourhoods of the rabbit (n = 5,253 neighborhoods) and mouse atlas (n = 14,034 neighborhoods). b ) Same plot as in Fig. 3d shown for all cell types. c ) Neighbourhoods of the mouse atlas (n = 14,034 neighborhoods) coloured according to their maximum correlation with any rabbit neighbourhood. General UMAP positions for a subset of cell types are shown. d ) Maximum correlation scores, grouped by the scRNA-seq sample (N = 19 embryos) of each neighbourhood index cell. Samples are ordered by mean maximum correlation and coloured by the developmental stage.Annotations above the GD9 samples refer to the anatomical dissection. The lower and upper hinges of the boxplots relate to the first and third quartiles respectively. The center line denotes the median and the whiskers extend to the largest/smallest value no further than 1.5 times the inter-quartile range from the upper/lower hinge respectively. Outlier points are plotted if they exceed the ranges defined by the the upper and lower whiskers. The number of neighbourhoods linked to each sample and thus used to calculate each statistic is written along the x-axis. A - anterior section, M - mid section; P - posterior section; YS -yolk-sac/extraembryonic tissues; EP - embryo proper. Neighbourhood sizes, annotations and maximum correlation values are provided in the source data.

Extended Data Fig. 8 Neighbourhood comparisons along differentiation trajectories.

a–c ) Neighbourhoods associated with a ) allantois, b ) amnion and c ) blood differentiation trajectories are shown for the rabbit and mouse. Maximally correlated neighbourhood pairs are linked, with the strength of correlation indicated with line colour. Neighbourhoods are coloured by annotated cell type. Neighborhoods in b , c are represented in the UMAP embedding, whereas in a , neighborhoods are positioned according to a ForceAtlas2 graph layout. d) Alluvial plot showing the proportion of rabbit gut tube neighbourhoods which form maximally correlated mappings with mouse neighbourhoods of different cell types. Rabbit neighborhoods represented in all panels were constructed from cells integrated across all samples (N = 19 embryos). Details of the neighbourhood mappings are provided in the source data.

Extended Data Fig. 9 Human and macaque cell type prediction with SingleR.

a ) Alluvial plot showing the changes to the original cell type labels after predicting annotations with a SingleR model trained on the rabbit atlas. Mappings only shown for predicted cell types with more than 10 cells. b ) UMAP of the CS7 human dataset (Tyser et al. 20 ) coloured according to the SingleR cell type predictions trained on the mouse atlas (1,195 cells, N = 1 embryo). c ) Same as in a for the classification of cells from the macaque in-vitro dataset (Yang et al. 44 ). d ) Same as in b for the Yang et al. 44 dataset (7,194 cells, N = 12 embryos). The predicted cell type annotations are available in the source data.

Extended Data Fig. 10 Ligand-receptor interactions and gene ontology reveal roles of visceral endoderm and mesothelium in yolk sac hematopoietic niche.

a ) Extended dot plot of CellphoneDB output reveals a large network of extracellular matrix protein interactions between the mesothelium and endothelium, as well as VEGF and FGF complexes. The order of the cell types along the x-axis indicates the order of the molecule1:molecule2 expression along the y axis. The size of the dot indicates the -log 10 (pvalue), while the color of the dot indicates the log 2 mean of the mean expression of the molecules. Of note, YS endothelium and mesothelium show a significant interaction between FLT1 and FLT family complexes with VEGFA, which plays a known role in haematopoiesis. Statistical analyses were performed using the one-sided permutation test as described in Efremova et al. 49 b ) Gene ontology analysis of the differential transcriptional expression of the visceral endoderm clusters and the mesothelium clusters reveal different roles in the yolk sac niche. Visceral endoderm cells score highly on nutrient transport roles like chylomicron assembly, cholesterol efflux, and cholesterol homeostasis (left). Mesothelium transcripts interact highly with the endothelium according to (A), and score highly on extracellular matrix organization and collagen fibril organization. This indicates a closer interaction with endothelium that is critical for the function of the yolk sac hematopoietic niche and the mesothelium provides a role in structure separate from the visceral endoderm cells. P-values are adjusted for multiple-testing. Differential expression results are available in the source data. Statistical analyses were performed using Fisher’s exact test on cells integrated across all samples (N = 19 embryos) where those cell types were present.

Supplementary information

Reporting summary, peer review file, supplementary tables.

Supplementary Table 1. scRNA-seq sample submission data. Supplementary Table 2. scATAC sample submission data. Supplementary Table 3. List of cell type annotations with a one-to-one correspondance between the rabbit and mouse Imaz-Rosshandler et al. 23 dataset. Supplementary Table 4. Cell type annotations with a one-to-many correspondance with cell types defined in the Imaz-Rosshandler 23 mouse dataset. Supplementary Table 5. Cell type labels that are variations of those defined in the Imaz-Rosshandler et al. 23 mouse dataset. Supplementary Table 6. Cell types defined exclusively in the rabbit dataset. Supplementary Table 7. Cell types defined exclusively in the Imaz-Rosshandler et al. 23 mouse dataset.

Source Data Fig. 2

Statistical source data.

Source Data Fig. 3

Source data fig. 4, source data fig. 5, source data fig. 6, source data extended data fig./table 2, source data extended data fig./table 3, source data extended data fig./table 4, source data extended data fig./table 5, source data extended data fig./table 6, source data extended data fig./table 7, source data extended data fig./table 8, source data extended data fig./table 9, source data extended data fig./table 10, rights and permissions.

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Ton, ML.N., Keitley, D., Theeuwes, B. et al. An atlas of rabbit development as a model for single-cell comparative genomics. Nat Cell Biol 25 , 1061–1072 (2023). https://doi.org/10.1038/s41556-023-01174-0

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The reality of rabbit research

Posted: by Mia Rozenbaum on 19/01/23

More on these Topics:

Rabbits are the classic poster child for outdated and badly portrayed cosmetic testing campaigns. But did you know that the use of rabbits – and other animals – for cosmetic testing has not been allowed in the UK or EU for more than a decade!

Testing cosmetic products and their ingredients on animals was banned in the UK in 1998 and across the EU in 2013 , and replaced with non-animal methods. To date, rabbits are still used in research , but only to further scientific and public health knowledge, and their care and welfare are strictly overseen by animal technicians and veterinarians.

Rabbits in research

In the UK, rabbits are involved in approximately 2.5% of all scientific procedures involving animals, most of which are used in antibody research , including analytics, diagnostics, and production.

The rabbit immune system can recognise a much broader range of antigens than rodents, while generating antiserum that contains a high volume of antibodies with increased sensitivity and affinity towards antigens of human origin. Their larger size also means they can produce significantly more antiserum than rodents. These characteristics often make rabbits more frequently used in antibody research compared to other animals.

Historically, rabbits were used to develop Louis Pasteur’s rabies vaccine . Today, rabbits still play a fundamental role in fighting infectious diseases. Rabbits display a general physiology, similar to that of humans, and like mice and rats, suffer from many diseases with human equivalents. For example, young rabbits often die from a disease called mucoid enteritis, a condition that shares disease mechanisms like those seen in individuals suffering from cystic fibrosis, and the diarrheal disease, cholera.

The World Health Organisation estimates that half a million children under five years old die each year because of diarrheal disease therefore, rabbits have been used by researchers at the University of Surrey and elsewhere to study this disease. Some of the bacterial organisms responsible for causing human disease do not cause clinical signs in rodents, necessitating the use of rabbits when investigating disease mechanisms and novel therapeutics.

“Rabbits were used because they gave the best representation of the human condition (in terms of diarrheal disease), as opposed to mice for example,” explains the University’s Named Information Officer (NIO).  

The rabbit has also been important in the study of cardiovascular disease, particularly hypertension and atherosclerosis, as they naturally develop arterial plaques in response to a high-cholesterol diet. Studies in rabbits remain key in many aspects of medical research, including cancer, glaucoma, ear infections, eye infections, skin conditions, diabetes and emphysema.

In the UK, the majority of animal procedures involving rabbits are classified as mild , meaning that the animal experiences short-term pain, similar to an injection or having a blood sample taken. However, a small number of experiments with rabbits involve moderate or severe suffering. Moderate experiments cause a significant disturbance to the animal’s normal state, for example, surgery carried out under general anaesthesia followed by painkillers during recovery. While severe experiments cause a major departure from the animal’s usual state of health and well-being, for example, long-term disease processes where assistance with normal activities such as feeding and drinking were required.

Huge efforts are made to minimise the pain and distress experienced by animals, but sometimes the experimental setting requires these procedures to take place. Research projects involving animals are only ever granted approval by the Home Office when there is not a suitable non-animal method, and when the potential benefits of the research outweigh the potential animal suffering.

Rabbit welfare in the laboratory

Many animals, including rabbits, are social animals that need room to exercise. “The image of the rabbit stuck in the cage is very much an outdated one,” the NIO at the University of Surrey told us.

“When rabbits were housed at the University a few years ago, they were kept collectively in floor pens with soft bedding and various enrichments to stimulate the animals”.

The University’s Named Animal Care and Welfare Officer (NACWO) added that “the rabbits were given dried vegetable bites to nibble on, tunnels to race into and hide, hay that they could eat, burrow and play with, different beddings to forage and cardboard that they could shred and keep busy with”.

However, some experiments may require that rabbits are kept singly housed, for example, if the animals are shedding infectious material. In this situation, rabbits are kept for short periods in cages in a biological containment facility, where they receive as many of the enrichments as can be safely given in that environment.

“Because of infection control concerns in the containment facility, it isn’t possible to have loose bedding on the floor of the cages” stated the NACWO. “But we do continue to cater for their needs by giving them raised areas to climb on so they are using their legs and building muscle, hay to nest with, and a shelter so the animals can hide, for example.”

Over the last five years, floor pens, or equivalent social housing systems, have become the norm in the UK and are a welcomed standard for housing rabbits.

“You see that the animals are a lot more relaxed in these housing systems, just by the way they react when anyone enters the room,” explains the NACWO. “The floor pens take up a lot more space and are more difficult to clean, but they are worthwhile. Even commercial rabbit breeders, from which we receive the animals, are keeping their rabbits in groups for welfare purposes” added the NIO.

A culture of care

“Rabbits are social animals that are often kept as pets. Working and interacting with them in a floor pen setting where they are relaxed and comfortable with their handler is very rewarding,” shares the NACWO at the University of Surrey. “We feel empathy for the animals, and recognise and appreciate their individual characters. It is a real pleasure and privilege to work with them.”

The animal technicians also engage in activities with the rabbits, to improve their quality of life, even when they’re not involved in a research protocol.

“There are many activities that are put in place to keep the animals stimulated, and the animal technicians at the University of Surrey spent a lot of time with them,” explains the NACWO.

The animal technician’s also make sure the animals are at ease with handling. Because the rabbits are part of research experiments, they are often held, moved about and checked. They need to be comfortable in different settings.

“We use positive reinforcements in the research setting so the rabbits are, for example, eager to step on scales or trolleys to get treats, or comfortable around noises in the research environment,” further explains the NACWO. “Taking the time to get the animals used to their immediate environment helps the animals be more relaxed, and this makes it easier for the researchers working with them to collect data.” ​​​

The positive impact of better animal welfare on science

The importance of good housing and husbandry is recognised in legislation and guidelines on the use and care of animals in science. Having less stressed animals and better welfare also has a positive influence on the resulting science.

“It is easier to interact with the animals and generate reproducible data when they are at ease in their environment, less stressed and well cared for,” explains the NIO. “It doesn’t necessarily change how the pathogen causes disease, but stress could suppress or enhance normal physiological processes and impact infection outcomes, leading to more variable data. In addition, it is easier to spot abnormal behaviours in healthy animals.”

Good animal welfare is intrinsic for good science. It improves the quality of research data derived from laboratory animals, their validity as models of human disease, the number of animals required to reach statistical significance, and the reproducibility of in vivo studies. Animal welfare science that explores the well-being of animals that are managed by humans, helps improve animals' lives in an evidence-based way, but also improves the science that is backed by these research animals.

Read more about rabbits in scientific research.

Last edited: 23 January 2023 15:50

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Dario d’Ovidio, Ludovica Pierantoni, Emilio Noviello, Federica Pirrone, Sex differences in human-directed social behavior in pet rabbits, Journal of Veterinary Behavior, Volume 15, 2016, Pages 37-42, ISSN 1558-7878, DOI: https://doi.org/10.1016/j.jveb.2016.08.072

Dobos, Petra, Laura Nikolett Kulik, and Péter Pongrácz. “The amicable rabbit–interactions between pet rabbits and their caregivers based on a questionnaire survey.”  Applied Animal Behaviour Science  260 (2023): 105869. DOI: https://www.sciencedirect.com/science/article/pii/S0168159123000412

Environmental Enrichment

Claire Speight (2016) Environmental Enrichment for Pet Rabbits – How Can the RVN Help Educate Owners?, Veterinary Nursing Journal, 31:5, 144-148, DOI:  10.1080/17415349.2016.1153990 Obesity

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Bradbury, A. G., and G. J. E. Dickens. “Appropriate handling of pet rabbits: a literature review.”  Journal of Small Animal Practice  57.10 (2016): 503-509. DOI: https://doi.org/10.1111/jsap.12549

McIndoe K, Saunders R, Blackwell E, Rooney N. The effect of blindfolding and swaddling on the stress response to handling in domestic rabbits.  Animal Welfare . 2022;31(1):27-36. doi: 10.7120/09627286.31.1.003

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Mee, Grace, et al. “Owner demographic factors are associated with suitable pet rabbit housing provision in the United Kingdom.” Veterinary Record 190.12 (2022): e1736.DOI: https://bvajournals.onlinelibrary.wiley.com/doi/abs/10.1002/vetr.1736

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Rescue, Rehoming, Population Statistics

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Clare F. Ellis, Wanda McCormick & Ambrose Tinarwo (2017) Analysis of Factors Relating to Companion Rabbits Relinquished to Two United Kingdom Rehoming Centers, Journal of Applied Animal Welfare Science, 20:3, 230-239, DOI:  10.1080/10888705.2017.1303381

Cristina Díaz-Berciano & Miguel Gallego-Agundez (2022) Abandonment and rehoming of rabbits and rodents in Madrid (Spain): A retrospective study (2008-2021), Journal of Applied Animal Welfare Science, DOI:  10.1080/10888705.2022.2162342

R.A. Ledger, The relinquishment of rabbits to rescue shelters in Canada, Journal of Veterinary Behavior, Volume 5, Issue 1, 2010, Pages 36-37, ISSN 1558-7878, https://doi.org/10.1016/j.jveb.2009.10.016 .

Williams, Joanne M., et al. ““Rabbit Rescuers”: A school-based animal welfare education intervention for young children.” Anthrozoös 35.1 (2022): 55-73. DOI: https://www.tandfonline.com/doi/abs/10.1080/08927936.2021.1944561

Socialization and Bonding

Burn C, Shields P. Do rabbits need each other? Effects of single versus paired housing on rabbit body temperature and behaviour in a UK shelter.  Animal Welfare . 2020;29(2):209-219. doi: 10.7120/09627286.29.2.209

Amber Foote (2020) Evidence-based approach to recognising and reducing stress in pet rabbits, Veterinary Nursing Journal, 35:6, 167-170, DOI:  10.1080/17415349.2020.1790449

Rioja‐Lang, Fiona, et al. “Rabbit welfare: determining priority welfare issues for pet rabbits using a modified Delphi method.”  Veterinary Record Open  6.1 (2019): e000363. DOI: https://doi.org/10.1136/vetreco-2019-000363

McMahon, Sarah A., and Ellie Wigham. “‘All ears’: a questionnaire of 1516 owner perceptions of the mental abilities of pet rabbits, subsequent resource provision, and the effect on welfare.” Animals 10.10 (2020): 1730.DOI: https://www.mdpi.com/2076-2615/10/10/1730

Ulfsdotter L, Lundberg A, Andersson M. Rehoming of pet rabbits (Oryctolagus cuniculus) in Sweden: an investigation of national advertisement.  Animal Welfare . 2016;25(3):303-308. doi: 10.7120/09627286.25.3.303

Skovlund CR, Forkman B, Lund TB, Mistry BG, Nielsen SS, Sandøe P. Perceptions of the rabbit as a low investment ‘starter pet’ lead to negative impacts on its welfare: Results of two Danish surveys.  Animal Welfare . 2023;32:e45. doi: 10.1017/awf.2023.41

Nicola Martin (2012) The state of UK pet rabbit welfare – what we can do about it, Veterinary Nursing Journal, 27:2, 66-68, DOI:  10.1111/j.2045-0648.2012.00146.x

Rooney, Nicola J., et al. “The current state of welfare, housing and husbandry of the English pet rabbit population.”  BMC research notes  7 (2014): 1-13. DOI: Article Link

Schepers F, Koene P, Beerda B. Welfare assessment in pet rabbits.  Animal Welfare . 2009;18(4):477-485. DOI:1 0.1017/S0962728600000890

Joerg Mayer, Susan Brown, Mark A. Mitchell, Survey to Investigate Owners׳ Perceptions and Experiences of Pet Rabbit Husbandry and Health, Journal of Exotic Pet Medicine, Volume 26, Issue 2, 2017, Pages 123-131, ISSN 1557-5063, https://doi.org/10.1053/j.jepm.2017.01.021 .

Kristensen, Annika Udengaard, et al. “Survey of the Husbandry, Health, and Welfare of Norwegian Pet Rabbits.” Journal of Advanced Veterinary Research 13.5 (2023): 767-775. DOI: https://advetresearch.com/index.php/AVR/article/view/1244

KATA, SIPOS, and BODNAR KAROLY. “The positive effects of pet rabbits on the study and school attitudes of high school students.” Lucrari Stiintifice, Universitatea de Stiinte Agricole Si Medicina Veterinara a Banatului, Timisoara, Seria I, Management Agricol 22.2 (2020): 159-163. DOI: https://www.researchgate.net/profile/Karoly-Bodnar/publication/346018215_THE_POSITIVE_EFFECTS_OF_PET_RABBITS_ON_THE_STUDY_AND_SCHOOL_ATTITUDES_OF_HIGH_SCHOOL_STUDENTS/links/5fb63b0a92851c933f3d6d80/THE-POSITIVE-EFFECTS-OF-PET-RABBITS-ON-THE-STUDY-AND-SCHOOL-ATTITUDES-OF-HIGH-SCHOOL-STUDENTS.pdf

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Rabbits in Research

New Zealand White rabbits, large albino rabbits, are the most common breeds of rabbits used in research, although other breeds, including Dutch Belted rabbits are used as well. Laboratory rabbits can be purchased from commercial vendors such as Covance, and range from $89-$292 per animal, depending on age and weight.

In 2019, about 37% of the rabbits used in research were subjected to procedures involving pain and distress. Rabbits are commonly used for toxicity and safety testing of substances such as drugs, chemicals and medical devices. They are used in skin and eye irritation studies, such as the archaic and painful Draize tests  for cosmetics, personal care, household products and other chemicals. This controversial use of rabbits resulted in some of the first large-scale protests against animal experimentation in the 1970s and 1980s and pushed the scientific community to search for  in vitro  alternatives.

A number of rabbit models have been developed to study human diseases, the most common being cardiovascular disease, cancer and AIDS. They have also been used as bioreactors for the production of pharmaceutical proteins. The rabbit is the breed of choice for polyclonal antibody production, tools commonly used in a variety of research methodologies.

Once in the laboratory, rabbits used in research in spaces depending on their weight, according to recommendations made by  The Guide for the Care and Use of Laboratory Animals . It is recommended that rabbits less than four pounds have a minimum floor area of one-and-a-half square feet per animal; rabbits up to nine pounds have a minimum floor area of three square feet per animal; rabbits up to 12 pounds have a minimum floor area of four square feet per animal, and; rabbits more than 12 pounds have a minimum floor area of five square feet   per animal. The  Guide  also recommends that cage height be at least 16 inches, and indicates that more cage height may be required to allow larger rabbits to sit up.

Rabbits used in research who are suffering from pain and distress may display a number of signs including lack of appetite, weight loss, self-mutilation, aggression, tremoring and/or vocalization.

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The rabbit consultation and clinical techniques

3.1. basic information about rabbits.

Biological data are summarized in Box 3.1 .

Basic biological data for rabbits

3.1.1. stress.

The effects of stress upon rabbits are significant (see Box 3.2 ). Catecholamines are released in response to stress and can initiate a number of problems. In extreme cases, catecholamine release can cause heart failure and death. Stress due to overcrowding has been used to induce cardiomyopathy in laboratory rabbits ( Weber and Van der Walt, 1975 ).

Stress in rabbits

Causes of stress of rabbits.

• • Pain and disease
• • Unfamiliar surroundings
• • Transport
• • Rough handling
• • Proximity of potential predators: dogs, cats, ferrets, birds of prey and, for wild rabbits, humans
• • A dominant companion and no means of escape
• • Inability to exhibit natural behaviour patterns, e.g. to forage, make a nest or interact socially
• • Poor husbandry: insufficient food, water and indigestible fibre, excessively high or low environmental temperature

Effects of stress in rabbits

Many of the effects of stress are linked to the release of catecholamines or corticosteroids and can be life-threatening:

• • Catecholamine release can cause heart failure and death. Stress due to overcrowding has been used to induce cardiomyopathy in laboratory rabbits
• • Stimulation of the sympathetic nervous system inhibits activity of the gastrointestinal tract. Gut motility is reduced, which can have a knock-on effect. Gut stasis, trichobezoar formation (hairballs), enterotoxaemia and mucoid enteropathy can all be linked with stress
• • Stress in rabbits causes a marked decrease in urine flow, renal plasma flow and filtration rate. Oliguria can last from 30 to 120 minutes
• • Stress can increase gastric acidity and cause gastric ulceration in rabbits
• • Stress is immunosuppressive. Rabbits suffering from dental disease have significantly lower lymphocyte counts than healthy rabbits
• • Stress affects carbohydrate metabolism. Handling alone can cause an increase in blood glucose to the order of 8.5 mmol/l. Blood glucose levels can be very high (20-25 mmol/l) in association with intestinal obstruction and other stressful diseases
• • Stress causes anorexia that, in combination with disruption to normal carbohydrate metabolism, can lead to hepatic lipidosis, liver failure and death

Ways to minimize stress in rabbits undergoing veterinary treatment

• • Use analgesics in any situation where the rabbit may be experiencing pain
• • Use quiet, gentle handling and sedate or anaesthetize rabbits for painful or uncomfortable procedures
• • Wrap rabbits in a towel for examination or procedures such as blood sampling
• • Keep rabbits away from the sight, sound and smell of predators, e.g. barking dogs, ferrets
• • Provide hay as bedding material for rabbits awaiting or recovering from surgery. Hay smells familiar and provides security for timid animals. It is also a source of indigestible fibre and foraging material
• • Consider hospitalizing a bonded companion with a sick rabbit
• • Minimize stressful procedures or devices, e.g. Elizabethan collars or nasogastric tubes

Stimulation of the sympathetic nervous system inhibits activity of the gastrointestinal tract. Gut motility is reduced, which can have a knock-on effect on caecal microflora and digestive function. Enterotoxaemia or gut stasis can result from any stressful situation. Mucoid enteropathy is associated with stressful situations such as weaning, parturition or re-homing.

Stress reduces renal blood flow in rabbits. In a study by Kaplan and Smith (1935) into the effects of diuresis and urine flow, a single dose of 50 ml/kg of water was given to rabbits before subjecting them to unpleasant or painful stimuli. The rabbits were subjected to electric shocks, loud bangs or being tied in a supine position on an animal board for long periods of time. In all cases the disturbing stimuli were immediately followed by a marked decrease in urine flow, renal plasma flow and filtration rate. Oliguria was frequently severe, lasting from 30 to 120 minutes. Some rabbits died in convulsions. The control group of rabbits that were not stimulated and remained undisturbed could withstand diuresis by increasing urine flow.

Stress increases gastric acidity. Gastric ulcers are a common post-mortem finding in rabbits, especially in those that have been anorexic prior to death. In a survey of 1000 post-mortem examinations by Hinton (1980) , 7.3% were found to have ulceration of the gastric mucosa that was related to the stress of the associated illness. Experimental stress ulcers have been induced in the gastric mucosa of laboratory rabbits by administering intraperitoneal injections of adrenaline ( Behara et al ., 1980 ).

Stress can alter the differential white cell count in any species. Rabbits are particularly susceptible to the effects of stress. A car journey to the surgery, a period in the waiting room next to a barking dog or the excitement of handling can be reflected in the blood picture. Adrenaline and cortisol affect the distribution of lymphocytes throughout the body. Administration of exogenous adrenaline to rabbits results in redistribution of lymphocytes from spleen and bone marrow to peripheral blood, lungs and liver ( Toft et al ., 1992a ). Conversely, exogenous corticosteroid administration results in a redistribution of lymphocytes from the peripheral blood, bone marrow and spleen to the lymphatic tissue in rabbits ( Toft et al ., 1992b ). Prolonged periods of stress cause lymphopaenia. Rabbits suffering from clinical symptoms of dental disease have significantly lower lymphocyte counts than healthy rabbits kept under free-range conditions ( Harcourt-Brown and Baker, 2001 ) (see Figure 6.1).

Carbohydrate metabolism is affected by stress. Handling alone can cause an increase in blood glucose to the order of 8.5 mmol/l. Blood glucose levels can rise to 20-25 mmol/l in critically ill rabbits, such as those with an intestinal obstruction. Disruptions in carbohydrate metabolism have potentially serious knock-on effects that can result in hepatic lipidosis, liver failure and death.

As a prey species, rabbits have many physiological and behavioural responses to adrenal hormones. The response to danger is either to ‘freeze’ or to jump and flee. Although the majority of pet rabbits are used to being handled by their owners and are not particularly stressed by clinical examination, there is always potential for them to suddenly spring up and attempt to escape. Broken bones or fractured teeth can be the consequence of a leap off the consulting table. Struggling rabbits can inflict injury by scratching with the hind legs or, very occasionally, biting.

Owners are often unaware of the stressful effect or the physical danger that is posed to their rabbit if it is sitting on their knee in full view of other animals in the waiting room. They may be next to potential predators such as ferrets, dogs, cats or birds of prey. Even the sound or smell of predators such as ferrets can be stressful. Loud noises, unfamiliar surroundings and car journeys all add to the stress levels of rabbits that are visiting the surgery. The effects of stress can be minimized by encouraging owners to leave their rabbits in the carrier in the waiting room, quiet gentle handling in the consulting room and the routine use of analgesics to all animals that may be in pain.

Key points 3.1

• • Rabbits are a prey species and susceptible to the effects of adrenal hormones. Stress can allow the flare up of latent infections and cause gastrointestinal hypomotility, reduce renal blood flow and increase gastric acidity
• • Pain, unfamiliar surroundings, loud noises and the proximity of predators can stress rabbits that are brought to a veterinary surgery
• • The effects of stress can be minimized by gentle handling and routine use of analgesics.

3.1.2. Reproduction

Rabbits are induced ovulators without a defined oestrus cycle, although females vary in sexual receptivity and a cyclic rhythm exists (see Section 1.4). Full sexual receptivity occurs every 18 days and is manifested by restlessness and increased chin rubbing. Does are fertile immediately after kindling, especially during the summer months. Breeders usually take females to the buck for mating rather than vice versa as they can be territorial and attack the buck if he is put in her hutch. Sometimes the two are introduced on neutral territory. In general, females are mated for the first time at approximately 5 months old and are not bred from over the age of 3 years ( Sandford, 1996 ). Mating takes place within a few minutes and can be accompanied by a scream from either party, which is deemed to be normal. Mating may be repeated after a couple of hours to improve the conception rate. Artificial insemination is a recognized technique in rabbit breeding. Pregnancy can be detected by abdominal palpation. The best time for pregnancy diagnosis is 10-14 days after mating when the fetal units can be felt as olive-sized masses. Fetal resorption can take place up to 20 days post-coitus. Mammary development occurs in late pregnancy. Radiographically, pregnancy can be detected after the 11th day.

Gestation takes 31-32 days. Some does remain sexually receptive during pregnancy and will continue to be mated by a male companion. During late pregnancy the doe may be seen carrying bedding material into her chosen nesting site. The nest is built from hay, straw or other bedding material. The quality of the nest varies between individual does and has a strong influence on the survival of the young. The doe will defend her chosen nesting site against potential intruders, especially if she is pregnant or lactating and can become aggressive towards owners, other rabbits or pets. Hair is pulled from the hip, dewlap and mammary glands to line the nest. She may consume less food at this point and should be tempted to eat, as pregnancy toxaemia is a risk during this period. Otherwise, the doe should be left undisturbed. Parturition usually takes place in the morning and lasts less than 30 minutes. When the entire litter has been born, the doe pulls more fur from her body to cover the litter in its nest. Does are particularly susceptible to disturbance in the first few days after parturition and may cannibalize the young. Inexperienced does sometimes mutilate them. The legs or ears may be attacked or the skin stripped over the neck, thorax or abdomen. Cannibalization and mutilation are most likely to take place on the day of parturition and may be an extension of eating the placenta. Sometimes young rabbits are born outside the nest or the doe rejects them. These kits will die from hypothermia unless they are warmed up and returned to the nest. The doe will usually accept them and the chances of survival are far greater if the kit is reared by its natural mother rather than being hand-reared by a human. It is advisable to remove other rabbits from the hutch during late pregnancy. Female companions can cannibalize the young and entire males will mate the doe within hours of her giving birth. Females can lactate and be pregnant at the same time and have a second litter within a few weeks of the first. The doe only feeds the young once or twice daily taking 3-5 minutes (see Section 1.4.). Owners often think the young have been deserted and need reassurance that it is normal for the mother to be out of the nest and that she may be particularly aggressive and protective during this period. Lactation takes place for approximately 5 weeks after parturition.

Baby rabbits are suckled once or occasionally twice daily by a mother and she spends very little time with them. In the wild, although the doe remains in close vicinity of the nest, she does not groom the young or keep them warm. Nests are hidden, well insulated and secure. The babies drink sufficient milk in 2-5 minutes to last 24 h. It is possible for baby rabbits to survive for more than 24-h intervals between feeds, which explains why females can rear litters that exceed their number of nipples ( Lang, 1981 ). Suckling normally takes place in the early morning and, if the doe does return to the nest to feed the young for a second time, then it is usually in the first few days after giving birth. The baby rabbits spend most of the day buried in the warmest part of the nest, tightly grouped together conserving heat and energy. After about 22 h, the whole group becomes active and makes its way to the surface ( McBride, 1988 ). When the mother arrives, she stands over the babies which suckle, changing nipples and position approximately every 30 seconds. After about 3 minutes, the doe leaves the nest and the babies urinate on the surface before digging themselves deep into the bedding to sleep for another 22 h. Young rabbits are totally dependent on milk until day 10. They are usually eating small amounts of solid food by day 15 ( Kraus et al. , 1984 ) and start to leave the nest and be weaned at about 3 weeks of age.

The glucose reserve of neonatal rabbits lasts approximately 6 h post partum. Hypoglycaemia results in rapid ketosis and death ( Kraus et al ., 1984 ). Passive immunity is obtained through the placenta, although there is some evidence that neonates absorb antibodies from their intestine in the first few hours after birth ( Brewer and Cruise, 1994 ). Rabbit milk has a low lactose content. It is of high nutritive value and the composition changes towards the end of lactation when protein and fat levels increase.

Rabbit owners are usually unaware of the natural lack of maternal behaviour by rabbits and become convinced that a nest of babies has been deserted. Constant interference and ‘checking to see if they are alright’ increases the likelihood of the mother cannibalizing the young in the first few days. There is also a misconception that all baby animals must be fed every 2-3 h, even during the night. If owners are concerned, the nest can be checked once a day and if the babies are warm, asleep and unwrinkled then they are being fed. Baby rabbits that are not being fed will be restless and crawling around on the surface of the nest. They take on a wrinkled appearance due to dehydration. It is possible to cross-foster orphaned rabbits to another lactating doe. It is not necessary to use any method for destroying the scent of the natural mother or human hand. Females do not make any distinction of young, even if they are of different colours or sizes ( Cheeke et al. , 1982 ). Ideally, older rabbits should be introduced to a younger litter. The fostered babies should be placed at the bottom of the nest with the natural kits on top.

3.1.3.1. Rearing orphans

Abandoned or orphaned wild or domestic rabbits can be hand-reared, although the mortality rate is high. Baby rabbits can be fed on powdered cat milk replacers. They will drink 2-30 ml of milk per feed, depending on how old they are. Baby rabbits should be fed when they are restless. Milk replacers are a nutritional compromise and do not match the composition of rabbit milk. Therefore orphan rabbits may need feeding two to three times daily, but care should be taken not to overfeed or force-feed them. Holding newborn rabbits on their backs simulates the natural nursing position. Hypothermic or moribund rabbits can be given fluids or milk replacers by stomach tube to correct hypoglycaemia. The babies should be kept warm and dry in a quiet place with suitable bedding material to burrow into. Shredded tissue paper or kitchen roll is satisfactory for making a nest that can be put in a hay-lined cardboard box and placed in a warm environment such as an airing cupboard.

Most suckling animals are stimulated to urinate and defaecate by the mother licking the perineum and lower abdomen. People that have successfully hand-reared orphans usually advise that baby rabbits should also be stimulated by rubbing the genital region after each feed. Female rabbits do not stay with their young and do not groom them so it may not be necessary to stimulate young rabbits in this way. However, it can do no harm and is therefore advisable.

Mortality can occur from aspiration pneumonia due to inhalation of milk replacer. A syringe with a small amount of tubing cut from a giving set is a satisfactory method of feeding orphans. Healthy babies suck the milk out of the syringe. Squirting milk into the mouth carries a risk of choking the rabbit. Enteritis is a potentially lethal complication of hand-rearing. Rabbits are unusual among young animals in having very few microorganisms in the stomach and small intestine while suckling ( Lang, 1981 ). An antimicrobial fatty acid or ‘milk oil’ is present in the suckling rabbit. It is produced by an enzymatic reaction in the doe's milk that takes place in the suckling rabbit's stomach ( Brooks, 1997 ). This ‘milk oil’ controls the gastrointestinal microbial contents of suckling rabbits and protects them from enteric infection. Orphan rabbits that are fed on milk from other species do not develop this antimicrobial factor and are therefore more susceptible to bacterial infections introduced during feeding. It is important that boiled water and sterile syringes and feeding tubes are used to feed orphans and that each feed is made up just prior to being given. Overfeeding can cause digestive upsets. In general, it is preferable to underfeed than overfeed. Small babies can soon make up their weight once they are weaned and able to digest solid food.

Baby rabbits can be offered hay and fresh food from about 18 days of age. Caecotrophs collected from healthy adults may be fed during weaning to colonize the intestinal tract with healthy bacteria and protozoa. It may be necessary to place an Elizabethan collar on an adult rabbit for a day or two to prevent them from eating the caecotrophs so they can be harvested. Weaning is a danger period for any young rabbit, especially orphans. Diarrhoea can result from colonization of the gut by pathogenic bacteria. Probiotics can be useful in this period, especially if no caecotrophs are available.

3.1.4. Pseudopregnancy

Pseudopregnancy mimics true pregnancy. Pseudopregnant does pull fur from their abdomen and chest, make a nest, develop mammary glands and aggressively defend their nesting site. Pseudopregnancy lasts for 16-18 days rather than the 31-32 days of true pregnancy. Because rabbits ovulate in response to sexual stimulation by another rabbit, proximity of a male or mating behaviour between two females housed together can stimulate ovulation and result in pseudopregnancy.

3.1.5. Advice on neutering

Neutering modifies sexual behaviour in rabbits but may not abolish it altogether. Increasing daylength can trigger social, sexual and even aggressive actions in neutered rabbits, although the behaviour is usually mild. In the spring, does may dig out a new burrow and males may have minor skirmishes. Copulatory actions can persist after neutering, as part of dominance or excitement behaviour. It is beneficial for rabbits to be neutered for similar reasons to the dog or cat. Neutering prevents unwanted pregnancies and pseudopregnancies and permits both sexes to be housed together. Male aggression is reduced or abolished so fight and bite wounds are minimized. Neutering also modifies scent marking by spraying urine or depositing faeces. Female reproductive disorders such as uterine or mammary neoplasia and endometritis occur frequently in the middle-aged doe. Spaying is indicated to prevent these diseases. Aggressive behaviour towards owners can be modified by neutering, especially if it is hormone related. Male rabbits make better pets if they are castrated. Entire bucks can attempt to mate their owner's legs or mount toys, mats or other household objects.

Although rabbits can be spayed or castrated at any age, approximately 5 months of age is the best time for both sexes. It is advisable to spay females after puberty but before maturity when large amounts of abdominal fat can complicate the surgery. Pre-pubescent females are difficult to spay because of their tiny uterus and ovaries that can be hard to locate. Males should be left until the testicles have descended. Motile spermatozoa appear in the ejaculate from about 4 months of age. After castration, the male can be considered sterile after a period of 4 weeks.

3.1.6. Leg rings

Pedigree rabbits are identified by an aluminium ring placed over the hock at 8-10 weeks of age. Some breeders use right or left legs according to the gender. Rings are purchased from the British Rabbit Council who keep records of the numbers. Different sizes are needed for different breeds, which are denoted by a letter that prefixes the ring number. The year of birth is also recorded on the ring. These rings should be removed as they serve no purpose in the pet rabbit and can trap hair and debris beneath them. Skin necrosis and secondary infection can set in (see Plate 1). In severe cases, the blood supply to the foot is cut off so the leg becomes gangrenous and has to be amputated or the rabbit euthanased. If the rings are not removed, owners must be advised to check them daily.

Key points 3.2

• • Pregnancy can be detected at 10-14 days after mating when fetal units can be palpated as olive-sized masses
• • Fetal resorption may take place up to 20 days post mating
• • Does should be left alone at the time of parturition
• • Mating can take place within a few hours of parturition
• • Orphan rabbits can be cross-fostered on to another lactating doe
• • Kitten milk replacers can be used as hand-rearing formulas for rabbits
• • Baby rabbits do not need feeding every 2-3 h. Two or three feeds a day are sufficient
• • Mating behaviour between two females or proximity of a male can induce pseudopregnancy
• • Neutering modifies sexual behaviour but may not abolish it altogether
• • Neutering is advisable to prevent unwanted pregnancies, reduce aggression and territory marking and remove the risk of uterine adenocarcinoma
• • Neutering can be done after 4-5 months of age.

Ring removal is almost impossible in the conscious animal. Sedation or general anaesthesia is required because leg rings cannot be slipped over the hock and need to be cut. Part of a wooden tongue depressor can be slipped between the ring and the leg to keep the fur our of the way and give some protection to the skin before removing the ring with a hack saw or small saw attachment on a power drill. Care is required to prevent the metal ring from overheating. Cotton wool soaked in water can be used periodically to cool the ring during removal.

3.2. Vaccination

3.2.1. myxomatosis vaccination.

Myxomatosis is a common disease in wild rabbits that can be spread to pet rabbits via insect vectors such as fleas and mosquitoes (see Section 16.6.1.). Those rabbits that are kept in gardens visited by wild rabbits are most at risk. At the present time there is only one type of vaccine available in the UK for the immunization of rabbits against myxomatosis (Nobivac Myxo, Intervet). Live vaccine is prepared from attenuated Shope fibroma virus grown on cell line culture. Shope fibroma virus naturally affects the cottontail rabbit Sylvilagus floridanus that is native to North America. It is antigenically related to myxoma virus and cross-immunity occurs. Shope fibroma virus is transmissible to the European rabbit Oryctolagus cuniculus in which it produces localized benign fibromas.

In order to stimulate an antigenic reaction and afford immunity, 1 ml of the vaccine is split between two routes; 0.9 ml is administered subcutaneously and the remaining 0.1 ml is given intradermally. Intradermal immunization produces maximum antibody response due to the presence of Langerhans cells within the dermis that act as antigen-presenting cells and increase the activation of T-helper cells. The intradermal route also provides some protection for the antigen by minimizing diffusion into the surrounding tissues and providing a depot effect. The dermis has excellent lymphatic drainage and intradermal injection maximizes exposure of immune cells to the antigen and the subsequent antibody response ( Stills, 1994 ).

The manufacturers recommend using the skin at the base of the ear for the intradermal injection and either administering the remainder of the vaccine subcutaneously at that site or through a separate injection in the scruff. It is also possible to administer both the subcutaneous and intradermal dose through a single injection in the scruff of the neck. The 1 ml dose is drawn into a syringe with a small (23-5 g) needle attached; 0.9 ml is injected into the subcutaneous tissue. The needle, orientated with the bevel up, is then slowly advanced into the overlying dermis and the remaining 0.1 ml injected into the dermis from underneath. A bleb of vaccine can be felt forming in the dermis if the skin over the end of the needle is pinched between the thumb and forefinger as the injection is made.

The vaccine can be given to rabbits over 6 weeks of age. It should not be given during pregnancy. Annual boosters are necessary, although in high-risk situations where pet rabbits are potentially exposed to insects or wild rabbits infected with myxomatosis, the interval between vaccinations can be reduced to 6 months. Myxomatosis tends to be a seasonal disease with outbreaks occurring in the late summer. The optimal time for vaccination is in the late spring to provide good immunity during the summer months. Insect control will also reduce the risk of infection.

3.2.2. Viral haemorrhagic disease

Viral haemorrhagic disease (VHD) is a highly infectious lethal disease of rabbits. It is caused by a host-specific calicivirus (see Section 16.6.2.). VHD virus is spread by oral, nasal and parenteral transmission and is present in urine and faeces from infected rabbits. The virus can survive for long periods outside the host. It is thought that wild birds carried infection across the channel from Europe to wild rabbits in this country. VHD may be transmitted directly from contact with wild rabbits or carried on footwear and clothing. Contaminated foods, such as grass or weeds picked from areas grazed by wild rabbits, can be a source of infection. Hutches and cages that have been occupied by an infected rabbit require thorough disinfection before a new rabbit is introduced. Ideally, only vaccinated animals should be brought in to infected premises. VHD virus can survive outside the host for 10-19 months at room temperature. Exposure to 2% Virkon for 2 h does not inactivate the virus, although 4% Virkon is effective; 1% sodium hydroxide or 10% household bleach are also effective disinfectants ( Gorski et al ., 1994 ; Goodly, 2001 ).

There is a vaccine against viral haemorrhagic disease that is available in the UK (Cylap, Fort Dodge). Rabbits over 10 weeks can be vaccinated with a single dose. It is safe to vaccinate pregnant animals with VHD vaccine. Boosters are given annually.

In contrast with myxomatosis vaccine the whole 1 ml dose should be given subcutaneously. Inadvertent intradermal injection can result in tissue reaction. After subcutaneous administration, it is advisable to massage the vaccination area thoroughly and advise the owner to do the same periodically over the next few hours. In this manner, the vaccine is dispersed in the subcutaneous tissues and is less likely to cause a reaction. Some judges penalize show rabbits that have an area of dermatitis or a scar, so it is important to make sure the owners are aware of the risk. According to the datasheet, accidental self-injection with the vaccine can cause a severe reaction in humans that could result in the loss of a finger.

3.2.3. Simultaneous administration of myxomatosis and VHD vaccine

It is tempting to administer both the myxomatosis and VHD vaccines during a single consultation. There are data to support the efficacy of simultaneous vaccination but no firm conclusions can be drawn because of differences in the type of vaccine. During an outbreak of VHD, 5000 rabbits in Poland were simultaneously vaccinated with myxomatosis vaccine (Myxovac M) and VHD vaccine (Cunivac) without complications. Controlled exposure to infection in the laboratory suggested that rabbits that were simultaneously vaccinated were immune to both diseases ( Gorski et al. , 1994 ). However, the manufacturers of the current VHD vaccine in the UK (Cylap, Fort Dodge) have pointed out that their vaccine is different from Cunivac so no conclusions can be drawn from the Polish experience.

At the present time, the manufacturers of both the myxomatosis and the VHD vaccine advise against simultaneous immunization. It is common practice to leave 2 weeks between the two injections.

Key points 3.3

• • Pet rabbits in the UK can be vaccinated against both myxomatosis and viral haemorrhagic disease (VHD)
• • Myxomatosis vaccine can be given to rabbits over 6 weeks of age. VHD vaccine is given to rabbits over 10 weeks of age
• • Myxomatosis vaccine should not be given to pregnant does. VHD vaccine can be given during pregnancy
• • Myxomatosis vaccine is given subcutaneously and a small amount (0.1 ml) intradermally
• • VHD vaccine must be given entirely subcutaneously and dispersed by massaging the injection area thoroughly
• • It is not advisable to administer both myxomatosis and VHD vaccine at the same time. At least 2 weeks should elapse between vaccinations
• • Myxomatosis vaccine administered during late spring offers protection over the summer months when the disease is prevalent in wild rabbits.

3.3. Behaviour problems and aggression

Like other species, rabbits respond to handling from an early age. A rabbit that associates humans with pleasurable experiences is less likely to be timid, scared or aggressive than a rabbit that is left to its own devices for most of the time and is chased or handled roughly when it does have human contact. A study into the effect of early handling has suggested that baby rabbits that are picked up and handled between the ages of 26 and 42 days are more willing to approach humans and will remain closer to them ( Der Weduwen and McBride, 1999 ).

Owners frequently seek advice about aggressive tendencies in their rabbits. Sometimes the reason for the aggression is obvious. Two entire males that are kept together are likely to fight and will need to be separated or castrated. Female rabbits are strongly influenced by their hormones and will vigorously defend their ‘nesting site’, i.e. a hutch or a run, and attack intruders, including other rabbits and humans. These rabbits may be quite docile when they are out of their hutch. For this reason, it is advisable to clean out hutches when they are unoccupied. Spaying usually cures this type of aggression, although it may take some weeks to settle down. Female rabbits can vigorously protect their young and aggressive behaviour can be extended to include the protection of a bonded companion.

Straightforward aggression is not the only reason for rabbits biting their owners. Occasionally fingers are mistaken for food especially if the fingers smell of sweets or biscuits. Overzealous grooming can result in a nibbling response. Young rabbits nibble objects as part of their development and can extend this exploratory behaviour to include their owners. People that smell of other rabbits or animals can be attacked as part of defensive territorial behaviour. In general it is preferable to approach nervous or aggressive rabbits from above. A rabbit that showed periodic aggression following periods of ‘stargazing’ was found to be seropositive for Encephalitozoon cuniculi (Harcourt-Brown, unpublished observation).

As in other species, pain can result in aggressive behaviour. A rabbit that is normally docile but starts to be aggressive should be examined carefully for a source of pain. Dental disease and the formation of sharp hooks on the molars can be extremely painful. Rabbits are also prone to painful musculoskeletal disorders such as arthritis or vertebral spondylitis.

Deafness has been reported as a cause of aggression in rabbits (Rabbit Health News 1991, 1993). Deaf rabbits may be startled by owners coming up on them unexpectedly and sometimes their response is to bite. Deafness can be caused by Psoroptes cuniculi infestation occluding the external auditory canal with mites and exudate. Many lop eared rabbits have external ear canals full of wax and debris anyway. In some rabbits, the tympanic bullae are of inspissated pus as a result of ascending Pasteurella multocida infection from the nasal cavity. Inspissated pus in the horizontal ear canal is a common post-mortem finding in many pet rabbits. Granulomatous encephalitis caused by Encephalitozoon cuniculi could cause deafness (see Section 12.4.).

Key points 3.4

• • Aggression in rabbits may be hormonal, territorial or a response to pain or alarm
• • Obese rabbits have high resting heart rates and can develop hypertension and cardiac hypertrophy. They are prone to developing fatal hepatic lipidosis if they become anorexic
• • High fibre diets that would result in weight loss in other species may not be effective in rabbits. Fibre is fermented by the caecal microflora to volatile fatty acids
• • Weight reduction can only be achieved in rabbits by providing a diet low in digestible fibre and high in indigestible fibre
• • Increased amounts of exercise are an important part of a weight reduction programme
• • There are no serious zoonotic diseases that can be spread from rabbits to healthy humans. Immunocompromised AIDS patients may contract Encephalitozoon cuniculi. Ringworm and ectoparasites such as fleas or Cheyletiella parasitovorax can cause skin lesions in humans
• • There are many techniques for handling rabbits. Wrapping them in a towel is an effective method of restraint
• • The immobility response (hypnosis) can be used as restraint for minor procedures but is not an alternative to either anaesthesia or analgesia
• • The immobility response can be initiated by placing rabbits on their back.

3.4. Obesity

Rabbits are animals that convert food efficiently and are often overfed by indulgent owners. They are used as laboratory models to study the effects of obesity in humans. Obese rabbits have high resting heart rates and can develop hypertension and cardiac hypertrophy ( Carroll et al ., 1996 ). Hyperinsulinaemia, hyperglycaemia and elevated serum triglycerides occur in obese rabbits and hepatic lipidosis develops readily after short periods without food, especially if the rabbit is stressed. Obese rabbits are poor surgical candidates.

Fat rabbits are unable to groom inaccessible parts such as the nape of the neck and the base of the tail. They are often unable to reach the perineum to consume caecotrophs. Fly strike and cheyletiellosis can be the result of inadequate grooming and soiled fur. Arthritic conditions are exacerbated by obesity. Sludgy urine and cystitis are also associated with inactive overweight rabbits (see Section 14.4).

Weight reduction can be difficult to achieve in rabbits. It is sometimes difficult to persuade owners that their rabbit has a problem. Many obese rabbits have very little exercise and eating is their main pastime. Owners often feel guilty about not allowing their pet out to exercise and worry about it being bored so they give it lots of food instead. A high fibre, low calorie diet that would result in weight loss in humans and other animals may not have any effect in rabbits. The caecal microorganisms can digest fibre to release volatile fatty acids that can be converted into fat. Only lignocellulose in the form of fibrous, lignified vegetation such as hay, straw or really tough weeds will pass through the digestive tract undigested.

Changing a rabbit's diet can be fraught with difficulty. Many rabbits are finicky, even obese ones, and will steadfastly refuse to eat anything at all if they are not offered their favourite foods. Starvation quickly leads to hepatic lipidosis in obese rabbits. Care should be taken at the outset to ensure that the rabbit is actually eating its new diet and is passing hard faeces. Quantities of cereal mixtures or pellets should be reduced or phased out over a couple of weeks. Eventually a diet of ad lib hay or grass with no concentrates can be given until the rabbit has lost weight. Small amounts of vegetables can be given as treat foods. As much exercise as possible is important.

3.5. Health risks from keeping rabbits

For a healthy human, the risk of serious infectious zoonotic disease from pet rabbits is negligible. The main health risks are associated with handling the animal. Rabbits can inflict nasty bites and scratches that can become infected. Owners can develop an allergy to rabbit dander.

Parasites can be transmitted from rabbits to humans. Fleas can be found on pet rabbits, although they are not usually the rabbit flea ( Spilopsyllus cuniculi ) but the cat or dog flea ( Ctenocephalides felis or canis ) caught from other pets in the household. Cheyletiella parasitovorax is transmissable to humans who handle infested rabbits. The mite causes erythematous pruritic lesions in humans, especially on the arms. Ringworm is occasionally encountered in pet rabbits. Asymptomatic infections have been reported ( Vangeel et al ., 2000 ).

Protozoal infections such as giardia ( Johnson-Delaney, 1996 ) can affect both rabbits and humans but transmission between species does not appear to occur. Toxoplasma gondii also affects both rabbits and humans but is only transmitted by eating undercooked rabbit meat. It is not transmitted through rabbit faeces. Encephalitozoon cuniculi has caused illness in humans but only immunocompromised individuals such as AIDS patients. There are isolated reports of human infections with organisms such as Salmonella or Bordetella bronchiseptica after contact with infected domestic rabbits ( Gueirard et al ., 1995 ). Obscure zoonotic infections occur in wild rabbits such as tularaemia ( Gill and Cunha, 1997 ), plague ( Yersinia pestis ) ( Cleri et al ., 1997 ), and listeriosis ( Broderson and Gluckstein, 1994 ).

3.6. Handling rabbits during the consultation

There are many techniques described for handling rabbits ( Burgmann, 1991 ; Quesenberry, 1994 ; Mader, 1997 ; Malley, 2000 ; Richardson 2000 ). Most pet rabbits are used to human contact and do not object to being picked up and examined. Rough handling and overzealous restraint can be counterproductive and alarm the rabbit and upset the owner. A quiet, gentle but firm approach is preferable, with the option to restrain the animal more firmly should the need arise. Rabbits seldom bite vets in the consulting room even if they bite their owners at home. Instead they can inflict nasty scratches with their powerful hind feet.

It is usually possible to lift pet rabbits out of carriers by placing a hand round either side of the chest and lifting them in the same manner as a cat or small dog. Placing a forefinger around each front leg can be helpful. Fractious or nervous animals can be lifted by the scruff with a supporting hand under the rear end. Very excitable or aggressive rabbits can be caught and removed from the carrier in a towel. Picking rabbits up by their ears is not acceptable and is no longer advocated, although it is recommended in some older texts. After being removed from the carrier, the rabbit can be held on the consulting table and observed while a clinical history is being obtained from the owner. To examine the perineum, the rabbit can be restrained in dorsal recumbency either by holding the scruff and lying the rabbit on its back or by cradling it like a baby in the arms of an assistant or the owner. Dorsal recumbency often evokes an immobility response. An alternative approach is to hold the rabbit upright and rest its rear end on the consulting table. There are many approaches and each clinician will find a method that suits them.

Wrapping a rabbit in a towel is a satisfactory method of restraint for examination of the face and mouth or for venepuncture. A large towel is placed on the table and the rabbit placed on top of it before being wrapped up so the whole body is enclosed with only the head exposed. An assistant, who may be the owner, is needed to hold the rabbit firmly against them or pressed gently on to the table. The front legs can be held. Jackson (1991) found that restraining laboratory rabbits by wrapping them securely in a towel not only reduced the stress of handling but also reduced the incidence of gastrointestinal stasis.

A good method of carrying a rabbit is to hold it with its face tucked in under the handler's arm. The close physical contact and covering the face appears to placate fractious animals.

3.7. Immobility response (freeze response or ‘hypnosis’)

The immobility response is often described as ‘hypnosis’, ‘the freeze response’ or ‘trancing’. Hypnosis can be a useful method of restraining rabbits for minor procedures ( Bivin, 1994 ). Although hypnosis has been described for more invasive techniques such as castration ( Okerman, 1988 ), it is not a humane alternative to anaesthesia or analgesia. There is controversy about placing conscious rabbits in dorsal recumbency at all. On one hand, some practitioners lie rabbits on their backs to perform a variety of procedures such as nail clipping, oral administration of medicines and even inserting mouth gags to examine or clip molars. On the other hand, there is a view that the immobility response occurs in stressful situations and that rabbits lying on their backs are terrified and waiting to be eaten. However, it is a useful technique in some situations. For, example, it is possible to immobilize conscious rabbits for long enough to take abdominal radiographs.

The immobility response is exhibited in prey species under conditions that are stressful or threatening. The phenomenon is characterized by lack of spontaneous movement and failure to respond to external stimuli for several minutes. In rabbits, there is hypotonia of flexor and extensor musculature, abolition of the righting reflex, depression of spinal reflexes, miosis, and a drop in blood pressure, heart rate and respiratory rate. An awareness of external stimuli is maintained, although there is a decreased response to noise and painful stimuli ( Danneman et al ., 1988 ). This trance-like state is induced in the laboratory by placing the rabbit in dorsal recumbency, covering its eyes with its ears and flexing its chin against the neck. The hind legs are stretched out for a few minutes before releasing the legs and gently stroking the chest and abdomen. As long as the head is flexed, the rabbit remains immobile and restraining devices have been designed to maintain this position ( Bivin, 1994 ). There are similarities between the immobility response and an opiate-induced state. The exact role of endogenous opioid systems is controversial and there are conflicting reports about the effects of naloxone which, theoretically, should prevent or reverse the hypnotic state ( Danneman et al ., 1988 ). Sudden noise or painful stimuli can interrupt the trance and there is considerable variation in individual susceptibility to the technique. In a study by Danneman et al . (1988) , the immobility response could not be evoked in 25% of rabbits. In the consulting room, some pet rabbits can be calmed and restrained by placing them in dorsal or lateral recumbency and gently stroking their stomach while speaking to them quietly. Blowing gently on their face or stroking the bridge of the nose can also be effective.

3.8. Clinical history

It is not always easy to elicit an accurate case history. Owners have preconceived ideas of the correct or incorrect way of keeping rabbits and will often wish to give the ‘right’ answer rather than a truthful one. For example, owners do not like to admit that the rabbit has not been out of its hutch for months or that it is weeks since they cleaned out its cage. When an owner says they feed ‘lots of greens’, this can mean half a cabbage leaf once a week or a diet exclusively of hay and vegetables. Misleading information can be given in response to enquiries about the amount of grass a rabbit eats. There seems to be reluctance on the part of owners to pick grass to feed to rabbits although they may be willing to put them out in a run on the lawn to graze. The length of time that a rabbit has access to grass varies considerably, from a couple of hours on two or three occasions during the summer months to several hours a day all year round. Owners often insist that their rabbit will not eat fresh greens, grass and weeds. Because the owner's perception is that the rabbit will not eat such food, they do not offer it. It is interesting how many hospitalized rabbits readily eat grass and dandelions despite their owner's protestations that their pet would not eat such a diet at home.

Recent changes in husbandry can be relevant. For example, a rabbit may not have learnt to use a new automatic drinker. A new batch of food may be unpalatable. Loss of a companion can result in anorexia and depression. Weight loss can result from bullying by a new dominant cage mate that prevents access to food.

Owners may describe symptoms such as tooth grinding or a change in demeanour. Some rabbits exhibit low grade neurological disorders such as head nodding when they are relaxed or appear unaware of loud noises. These behavioural clues are unlikely to take place in the consulting room when the rabbit is apprehensive and have to be elicited from the owner.

3.8.1. Breed incidence

Dwarf breeds appear to be predisposed to developing incisor malocclusion. Giant breeds are more susceptible to cardiomyopathy and arthritic conditions. The giant English and French Lops are prone to superficial pyoderma in the large skin folds that can develop under the chin and around the perineum. Entropion also occurs in these breeds. The thin fur on the hocks of Rex rabbits makes them susceptible to developing sore hocks and the short maxilla and ‘squashed in’ face of the Netherland Dwarf can alter the anatomy of the nasolacrimal duct so it is prone to blockage. Dwarf breeds appear to have a susceptibility to developing torticollis due to Encephalitozoon cuniculi infection ( Kunstyr and Naumann, 1983 ).

Young rabbits that are newly purchased are more likely to be affected by infectious diseases than the adult rabbit kept on its own. Newly weaned rabbits are susceptible to various enteric conditions. Colibacillosis is more prevalent in suckling rabbits and hepatic coccidiosis and mucoid enteropathy are most likely to occur in the post-weaning period. Stress predisposes young rabbits to pasteurellosis. Rhinitis is often seen in young rabbits that have been taken from breeding colonies and exposed for sale in a pet shop. Congenital malocclusion is seen in the young rabbit, whereas the incidence of acquired dental disease, neoplasia and musculoskeletal problems increases with age. Thymomas and a variety of skin tumours are among the other types of neoplasms that have been reported in rabbits. Although tumours are usually encountered in elderly patients, it is possible to discover neoplasms in young animals. Lymphosarcoma has been reported in an 8-10-week-old rabbit ( Cloyd and Johnson, 1978 ).

3.8.3. Husbandry

It is important to find out if the rabbit lives on its own or with a mate. Fur chewing or fights can result in alopecia, wounds or abscesses. Does that are kept with other does or neutered males are more likely to suffer from false pregnancies than those that are housed on their own. Contact with wild rabbits is also a relevant part of the history. It is not unknown for does to dig out of their enclosure, escape and return or be found a few days later. Myxomatosis or pregnancy can be the result. Rabbits kept in enclosures or hutches can be visited by wild rabbits, especially during the night. There is often a pile of droppings as evidence of the visit.

House rabbits are prone to chewing household fixtures. Heavy metal toxicity or electrocution is more likely to occur in a house rabbit than one kept in a hutch outside. They are also at a greater risk of traumatic injuries and fractures. The material that is used in the litter tray is also an important part of the history. For example, pine shavings can cause hepatotoxicity or clay materials can cause caecal impactions.

Hutch rabbits are more likely to suffer from diseases of neglect. It is not uncommon for hutch rabbits with long-standing conditions such as large abscesses, advanced dental disease, and terminal neoplasia to be presented with no clinical history at all. Hutches kept in stuffy sheds predispose to pasteurellosis and upper respiratory tract infections. Hutches exposed to severe weather conditions predispose to heat stroke or stress-related diseases such as gastric stasis following predator attack, a thunderstorm or severe frost.

3.8.4. Eating and drinking

Rabbits normally drink 50-100 ml/kg/24 h ( Brewer and Cruise, 1994 ). The composition and water content of the diet affects this quantity. Rabbits that eat fresh greens may not drink at all ( Cheeke, 1987 ). High protein diets require a high water intake. Fibrous, dry foods absorb water in the intestinal tract and therefore increase thirst. During periods of water deprivation, food intake is reduced, sometimes to the point of anorexia. Conversely, food deprivation results in an increase in thirst with rabbits drinking up to 650% more water ( Brewer and Cruise, 1994 ). Some rabbits never learn to use automatic drinkers and will only drink out of a bowl. Water deprivation eventually leads to dehydration and prerenal azotaemia.

3.8.5. Urination and defaecation

Many owners do not know whether their rabbit is urinating or defaecating normally, especially if it is kept in a hutch or lives with another rabbit. Faecal consistency, size and output are an important part of the clinical history. Sometimes there are some faecal pellets in the carrier that can be examined during the consultation. A healthy rabbit, that is eating well, passes large quantities of hard faeces and eats the soft caecotrophs (see Table 3.1 ). The number of hard faeces varies with the fibre content of the diet. A healthy 2.5-3 kg rabbit produces about 150 hard faecal pellets a day ( Lowe, 1998 ). Hard pellets can be expelled at any time but are always produced overnight. Absence of hard faeces is indicative of anorexia or reduced intestinal motility. Small faecal pellets are produced following periods of reduced food intake.

Significance of faecal output

Observant owners may see their rabbit ingesting caecotrophs from the anus. Uneaten caecotrophs are sometimes seen as shiny clusters of dark pasty pellets in the bedding of normal animals. Uneaten caecotrophs are often interpreted as diarrhoea. This is not surprising as caecotrophs have a strong smell and a soft consistency in comparison with the hard faecal pellets. Obesity, spinal problems and dental disease are among the many reasons for caecotrophs to be left uneaten (see Figure 10.6). Uneaten caecotrophs can become entangled in the fur under the tail and form an unpleasant, malodorous faecal mass. Changes in the consistency of caecotrophs can follow ingestion of a new food or a succulent item such as lettuce or fruit. Soft, sticky or liquid caecotrophs may be passed. It is thought that this is due to alterations in the caecal microflora. Rabbits on a high fibre diet have a healthy caecal microflora that can withstand dietary changes. Uneaten caecotrophs are not life threatening although they are unpleasant for the owner and rabbit, and predispose to other conditions such as superficial pyoderma, fly strike and problems with urination due to inflamed painful perineal skin (see Section 9.7.2, Section 10.6, and Section 14.4.3).

Enteritis is signified by excretion of faecal material that cannot be identified as either hard or soft faeces. Microscopic examination of the faecal material can be helpful (see Section 6.8). Caecotrophs consist of a paste that is rich in bacteria that are easily seen on a faecal smear stained with gram's stain. Hard faeces consist of particles of indigestible fibre and little else. Sometimes it is necessary to hospitalize the rabbit to observe faecal output.

Urination should take place with no pain or discomfort. Normal rabbit urine varies considerably in its visual appearance. The colour can vary from the pale yellow colour that is familiar in other species through a range of oranges and brown to a deep red that can be mistaken for blood. The colour depends on the diet and is the result of the excretion of plant pigments. Vegetables such as cabbage, broccoli and dandelions often result in the excretion of red urine. There are clinical conditions such as urolithiasis and uterine disorders that will cause haematuria. Examination of the urine with a dipstick differentiates between blood and plant pigments. Alternatively, a Wood's lamp can be used as urinary pigments fluoresce when exposed to ultraviolet light ( Benson and Paul-Murphy, 1999 ).

Normal rabbit urine can be cloudy due to the presence of calcium carbonate precipitates. The rabbit kidney is adapted for the excretion of large amounts of calcium (see Section 1.6.7). Intestinal absorption is related to the calcium content of the diet and excess amounts are excreted by the kidney. Therefore the amount of calcium carbonate precipitate varies with the calcium content of the diet. The hydration status of the animal and pH of the urine also affect the amount of precipitate. The urine can be clear during periods of high calcium demand such as growth, pregnancy or lactation. A small amount of precipitate is a good sign as it reflects adequate calcium content in the diet. Excessive precipitate can form a thick sludge, especially in the bladder of rabbits that do not urinate frequently (see Section 14.4). High dietary calcium levels exacerbate the problem. Cystitis and urinary incontinence can be the result. It can be difficult to differentiate between normal calcium carbonate deposits and abnormal amounts of sludge. Normal rabbit urine is often radiopaque. Calcium carbonate deposits in the urine of an otherwise healthy animal with no sign of urinary tract disease can be ignored. Similarly, triple phosphate crystals can be a normal finding in rabbit urine.

3.9. Clinical examination

A list of differential diagnoses for some commonly encountered conditions of pet rabbits is given in Table 3.2 .

List of differential diagnoses for some common conditions in pet rabbits

3.9.1. General condition

The general health of a rabbit can be assessed by the state of its coat and its body weight. Obese animals are prone to grooming difficulties, sludgy urine, cystitis, parasitic skin disease, perineal soiling from uneaten caecotrophs, fly strike, cardiovascular disease, arthritis, hepatic lipidosis and death. At the other end of the scale, weight loss is a signi ficant clinical finding as rabbits are seldom given insufficient food unless there is serious neglect taking place. Dental disease, gastrointestinal hypomotility, renal or liver disease or neoplasia can cause weight loss despite the rabbit looking lively and well to its owner.

3.9.2. General demeanour

A healthy rabbit is responsive and alert with its nose constantly twitching. The response to pain is to become quiet, immobile and oblivious of the surroundings. Visceral problems such as gut stasis, or urolithiasis appear to be more distressing to rabbits than the abscesses or fractures. Occasionally, overt signs of pain such as tooth grinding can be evident. This is usually associated with visceral pain especially impactive intestinal problems such as mucoid enteropathy (see Section 10.9). Intestinal obstruction is associated with severe depression and immobility, which gives a characteristic clinical presentation (see Box 3.3 ). The presence of spurs on the molars that traumatize the sensitive mucosa of the tongue is also very painful for rabbits.

Intestinal obstruction in pet rabbits

Intestinal obstruction in pet rabbits gives a characteristic clinical presentation. The most common cause of obstruction is a felt of hair that is groomed out of the coat, especially the hind feet, during moulting. Dried pulses, foreign objects, tumours, tapeworm cysts are among other causes of obstruction (see Chapter 10). If the condition is recognized early and surgery is performed promptly, there is a reasonable chance of success. If the condition is not recognized and treated, the rabbit will die unless the foreign body happens to pass into the colon.

Presentation

• • Sudden onset. The rabbit was well until a few hours before presentation
• • Severe mental depression. The rabbit is unresponsive and totally anorexic
• • Abdominal distension. The owners may have noticed a bloated appearance although it may be masked by a thick coat
• • Palpably distended stomach. A ‘strange feeling’ or distended abdomen or abdominal pain is a clear indication for abdominal radiography
• • Shock, dehydration and collapse. Depending on the site of the obstruction, the rabbit's condition will deteriorate rapidly.
• • Abdominal radiographs are diagnostic. A stomach distended with gas and fluid is clearly visible (See Figure 10.5, Chapter 10). A section of gas-filled intestine can usually be seen radiographically, proximal to the site of obstruction. If the obstruction moves into the colon, gas can be seen in the caecum and proximal colon
• • Other causes of gastric dilatation include mucoid enteropathy or dysautonomia, both of which carry a poor prognosis
• • Abdominal palpation. An impacted organ, intussusception or foreign body may be palpable, especially if the rabbit is anaesthetized or moribund
• • Prompt exploratory laparotomy is indicated.
• • Motility stimulants are contraindicated prior to surgery. Postoperatively, cisapride or metoclopramide are required to prevent ileus
• • Effective analgesia is important. Low dose fentanyl/fluanisone (Hypnorm, Janssen 0.2 ml/kg) provides analgesia, sedation and vasodilation that facilitates intravenous fluid therapy
• • Decompress the stomach by passing a stomach tube (a stomach tube should remain in place throughout surgery). This can usually be done after the rabbit has been sedated
• • Fluid therapy. Intravenous (or intraosseous) fluid therapy is essential. Subcutaneous fluids will be ineffective in restoring and maintaining blood pressure and correcting dehydration and electrolyte imbalances
• • Anaesthesia, gradual mask induction with isoflurane is recommended. Anaesthesia and perioperative care are described in Chapter 5
• • Enterotomy. Midline incision. The obstruction is often easy to find. The gas-filled small intestine can usually be identified and followed to the site of the obstruction. (Basic surgical principles in rabbits are described in Chapter 15). Fine suture material (5/0 or 6/0 PDS or Monocryl) is required to repair the intestinal incision. A set of fine instruments is essential (a detailed description of surgical procedure is given in Chapter 10).

3.9.3. Gait

It is often helpful to allow the rabbit to hop around the consulting room floor, providing the owner and practitioner are confident that the animal can be caught again. Slippery vinyl is a difficult surface for rabbits to move about on. Placing a large towel on a slippery floor aids assessment of the patient's gait. Abnormal gait associated with spinal problems or fractures may be discovered. Neurological deficits can become evident and the rabbit's general demeanour is easier to assess.

3.9.4. Sex, age and sexual maturity

Rabbits can be difficult to sex, especially when they are immature, wriggling and presented individually so no comparison can be made. It is often simpler to sex neonates than animals of 4-6 weeks of age. Adults are usually straightforward because entire males have prominent descended testicles. Bucks tend to be larger and have a broader head than does. Mature, entire males develop a thick skin especially around the scruff and on the dorsum. Females often have a dewlap as a secondary sexual characteristic although some males can develop quite a pronounced dewlap especially if they are castrated or overweight. Pressure on the genital orifice everts either the penis or the vulva. The vulva can look like a small penis to the novice but is shorter, less round and has a slit like opening rather than the circular orifice of the male (see Figure 3.1 ). Testicles descend at 10-12 weeks, although they can be retracted into the abdomen during periods of ill health or starvation.

Inguinal skin folds and male and female genitalia. In both sexes, deep skin folds lie on either side of the genital orifice. These folds contain scent glands. It is normal for the folds to contain a waxy, odorous exudate. In (b), a brown exudate can be seen. Rabbits can be sexed by applying gentle pressure on the genital orifice to extrude the genital organ. (a) Male genitalia : In the male, the penis is extruded. Testicles can usually be seen in the scrotal sacs of sexually mature rabbits (> 10-12 weeks) although they can be retracted during periods of stress, illness or shortage of food; (b) Female genitalia : In the female, the vulva is extruded. The vulva can look similar to a small penis but is shorter, less round and has a slit like opening rather than the circular orifice of the male.

There are conflicting reports on the life expectancy of rabbits. Five to 7 years is the life span given by Gillett (1994) with a comment that rabbits can live to be 15. Many pet rabbits live longer than 7 years and can easily attain 11-12 years, although geriatric diseases are common in this age group.

It is difficult to age living rabbits with any degree of accuracy. The epiphyseal line in the tibia closes at approximately 9 months of age. The epiphyses of the lumbar vertebrae close much later. Counting the adhesion lines in the periosteal zone of the mandible by histopathological examination can be used to age mature rabbits accurately ( Henderson and Bowen, 1979 ) but this is not possible during life. The deciduous teeth are shed at birth and so the only criteria to make an assessment of age during clinical examination, are the size and appearance of the rabbit, both of which vary according to breed and state of health. The claws of the rabbit do not project beyond the fur until the rabbit reaches maturity ( Sandford, 1996 ) but this age varies according to breed and size. Fanciers may be able to give an indication of age by feeling the ears that are soft in the young rabbits and become tougher with age ( Sandford, 1996 ). Pedigree rabbits may have rings over their hocks on which the year of birth will be recorded. Smaller breeds mature at 4-5 months of age and the larger breeds mature at 5-8 months ( Donnelly, 1997 ). Bucks reach puberty later than does and so immature females that are housed with their brothers are unlikely to conceive even though he may mount and appear to mate her. Obviously, the two sexes should be separated or neutered at this stage if pregnancy is to be prevented.

3.9.5. Examination of the skin, fur and mucous membranes

A healthy rabbit will spend a lot of time grooming. Rabbits that are kept together groom each other, especially around the head. There are many clinical conditions that can prevent a rabbit from licking and grooming properly, which are manifested by a dull coat full of dead hair and skin debris. Combing through the fur with a flea comb gives an idea of the amount of dead hair and debris and also reveals the presence of fleas, flea dirt or mites. Mites can just be seen with the naked eye especially under good illumination. A magnifying glass can be used to examine the fur thoroughly. Microscopic examination of skin brushings confirms their presence and gives an idea of numbers. Most rabbits have some degree of infestation, which is not always significant (see Section 9.14.2). The area of skin between the shoulder blades and above the base of the tail are difficult for the rabbit to reach and groom, especially if it obese or has limited flexibility due to spondylosis (see Figure 3.8 ). Cheyletiellosis often starts to become evident on the back of the neck and along the dorsum. During the summer, soiled fur at the base of the tail or the perineum must be examined closely for the presence of maggots.

Sites for venepuncture and intraosseous fluid therapy plus difficult to groom areas. The jugular, cephalic and saphenous veins are in similar positions to those of other domestic animals such as dogs and cats. All these sites can be used for blood sampling and intravenous injections in rabbits. The jugular vein is the greatest in diameter and is the best site for taking blood samples. The ear vein is also satisfactory in large breeds or for collecting small volumes. The needle and syringe may need to be heparinized as rabbit blood clots very quickly.

Suggested techniques: (Further information is given in Section 3.12 , Clinical techniques). Jugular blood sampling: good restraint is required for taking blood from the jugular vein. The rabbit should be wrapped in a towel, placed on the edge of a table and held by an assistant. The head is raised and held back, either by the assistant or by the person collecting the blood. It is important to ensure that the head is held straight. The fur over the jugular furrow is clipped off. Usually, the vein is easily visualized and can be raised by placing a finger at the thoracic inlet. A good quality sample of 5-10 ml of blood can be collected quickly from this site without either haemolysis or clotting.

Intravenous fluid therapy. A simple method of venepuncture for intravenous fluid therapy is to use a 21 gauge or 23 gauge butterfly catheter (see Section 3.12.4.2 ). One wing is removed before inserting the needle, bevel up, into the marginal ear vein (caudal auricular vein). The remaining wing is ‘superglued’ to the fur on the ear after the needle has been inserted into the vein. The wing provides a large surface area of contact with the ear. In sedated or moribund rabbits, no bandaging is necessary to keep the needle in place, although a piece of bandage tied around the rabbit's neck can be used to hold the giving set out of the way. An intravenous catheter may be used instead of the butterfly set, but is not as satisfactory because the wing does not have as large a surface area for the bonding agent. Alternative sites for intravenous fluid therapy are the cephalic and saphenous veins.

Intraosseous fluid therapy . In all intraosseous sites, a spinal needle is preferable because the stylet prevents bone clogging the needle. A spinal needle is stronger and more able to penetrate the bone.

Possible sites for intraosseous administration:

• 1. Proximal humerus: this is the easiest site for access to the medullary cavity. An imaginary straight line is made using the greater trochanter of the humerus and the elbow joint as landmarks. The needle is inserted through the greater trochanter and directed along the imaginary line to penetrate into the medullary cavity.
• 2. Tibial crest: an intraosseous catheter can be inserted just caudoproximal to the tibial crest. However, the lateral wall of the tibial cortex curves medially and the needle must be directed towards the medial aspect of the tibia in order to penetrate the medullary cavity. If the needle is mistakenly inserted along an imaginary straight line towards the hock joint, it will go into the cortex of the tibia and miss the medullary cavity.
• 3. Proximal femur: this is the least satisfactory site for intraosseous fluid therapy because of the well-developed trochanteric fossa. This can be seen on the caudal view of the femur. The path of an intraosseous catheter has to pass through this fossa to gain access to the medullary cavity. Therefore, to gain access to the medullary cavity three layers of cortical bone must be penetrated.
• 4. Difficult to groom areas. The areas of skin that are difficult for a rabbit to reach and groom are shown as green shading. Obesity or other flexibility problems hinder grooming in these areas and allow dead hair, skin debris and parasites to accumulate. Signs of skin disease often begin at these sites. The area between the tail and the dorsum can become contaminated by urine, faeces and is often the site that flies choose to lay their eggs. These are the areas that owners should pay particular attention to when grooming their pet.

The area under the dewlap is prone to superficial pyoderma, predisposed by factors such as poor hygiene, dental disease or obesity. Some rabbits are unable to drink without immersing their dewlap in the water bowl. Excess salivation as a result of dental disease can result in a wet dewlap that is prone to bacterial infection. Fat rabbits with excessive skin folds and large dewlaps experience problems grooming and may lick the cranial surface of the dewlap obsessively as a type of displacement activity because they cannot groom other areas such as the underside of the dewlap or the perineum which is infected, inflamed and sore.

The forelegs are used to clean the face. Examination of the inner aspect of the carpus and metacarpus may show saliva staining indicative of dental disease. Dried mucopurulent material can be found in rabbits with ocular or nasal discharges. Examination of the fore and hind limbs may show evidence of ulcerative pododermatitis. An area of thin, hairless skin over the point of the hock is not unusual. It is protected by thick fur that is directed across it.

Felts of densely matted hair are a cause of intestinal obstruction if the rabbit ingests them during grooming. Large felts can accumulate on the plantar aspect of the hind feet. Owners should be advised to groom these animals daily and ensure that loose felts of hair are removed. Rabbits with dental problems or long-haired breeds such as Angoras are especially at risk.

3.9.6. Examination of the perineum

Examination of the perineum confirms the sex of the rabbit and gives an indication of general state of grooming. Urine scalding, vaginal discharges, adherent caecotrophs, fly strike, perineal fold dermatitis or diarrhoea may be evident on examination of this area (see Figure 3.2 )

Causes of perineal soiling in pet rabbits. A healthy, short-coated rabbit will meticulously groom its perineum and keep it clean. There are many inter-relating factors that can prevent effective grooming of this area and result in matted, soiled fur with or without inflamed underlying skin.

The two deep folds of skin on either side of the anal orifice are the inguinal glands that are normally filled with a yellow-brown odiferous deposit (see Figure 3.1b ).

The perineum is an extremely sensitive area in rabbits. Pain caused by infected, inflamed perineal skin can lead to urine retention, urethritis, cystitis and/or urinary incontinence. Urine scalding can also be due to urogenital disease or indicative of other problems such as vertebral spondylitis, sore hocks or arthritis which prevent the rabbit positioning itself correctly to urinate (see Section 14.4.3). Neurological deficits, abdominal pain or generalized weakness can also lead to urine scalding or perineal soiling. Skin inflammation in the perineal area may be caused by uneaten caecotrophs that have become adherent to the fur and caused superficial pyoderma of the skin beneath. Obesity, dental disease and arthritis prevent grooming around the perineum so the fur becomes matted, soiled and infected. This starts a vicious circle that can be broken by clipping and cleaning the perineal area and treating the painful dermatitis (see Figure 9.1 and Section 9.7.3). Clippers can be used to remove most of the fur. A sharp pair of curved, pointed scissors is useful to tease out and cut matted hair around the genitalia and under the tail. Dead and matted hair can be combed out with a flea comb. It is very easy inadvertently to damage the delicate skin. Patience and the correct equipment are required. Sedation may be needed. The underlying reason for urinary incontinence, cystitis, grooming difficulties or uneaten caecotrophs needs to be addressed to prevent recurrence.

The appearance of the vulva alters according to the state of sexual receptivity. When the doe is non-receptive, the vulva is pale pink and dry. During receptivity, the vulva becomes swollen, moist and red, becoming darker until it is purple at the end of the receptive period. If the doe is mated, the vulva returns to a light pink colour in about 24 h.

Inflamed or crusty skin around the genitalia can be associated with Treponema cuniculi or ectopic Psoroptes cuniculi infestation. Ear mites can be transferred from the ears to the perineal folds during grooming. Examination of the external ear canal of affected rabbits reveals thick crusty exudate caused by P. cuniculi . Rectoanal papillomas can cause crusty lesions that protrude through the anal sphincter.

The hydration status of the rabbit can be assessed during examination of the perineum. Dehydration can occur in the absence of obvious fluid loss due to the redistribution of water and electrolytes associated with alterations of gastrointestinal motility. Although rabbits do not to take on a ‘sunken eyed’ appearance when dehydrated, the thin skin becomes wrinkled and loses its turgidity. The hairless scrotal skin of males is a useful site to assess hydration status by tenting the skin. The inguinal skin can be used in females.

Mucous membranes can be examined by looking at the colour of the nose or by lifting the lip to see the gums and tongue. Cyanosis is evident in advanced cases of cardiovascular or respiratory disease. Mild anaemia is more difficult to elucidate although extreme pallor is obvious.

3.9.7. Rectal temperature

The rectal mucosa is thin and easily damaged. Many practitioners do not routinely take the rectal temperature as part of their clinical examination because of the risk of trauma and the limitations in interpreting its significance.

Key points 3.5

• • Rabbits normally drink 50-100 ml/kg/24 h although the amount may vary with diet
• • Water deprivation results in anorexia
• • Food deprivation can increase thirst
• • Normal rabbit urine can be any colour from yellow, to brown orange or red
• • Normal rabbit urine is turbid
• • Immature rabbits can be sexed by everting the genital orifice. The female has a slit like vulva. The male has a penis. Testicles descend at 10-12 weeks
• • Female rabbits have a dewlap
• • It is difficult to age live rabbits with any degree of accuracy
• • Examination of the perineum is an essential part of clinical examination. Urine scalding or faecal soiling may be indicative of other diseases
• • Normal rectal temperature is variable: < 38°C can be considered subnormal. > 40.6°C is significantly high.

Normal rectal temperature of rabbits is 38.5–40°C (103.3–104°F). It is affected by factors such as environmental temperature and restraint. There is a slight seasonal variation with temperatures being higher in the autumn and winter than in spring and summer. Females have a slightly higher rectal temperature than males ( Pericin and Grieve, 1984 ). Temperatures below 38.0°C (100.4°F) can be considered subnormal and temperatures in excess of 40.6°C (105°F) are significant and indicative of pyrogenic infection ( Toth and Krueger, 1989 ) or heat stroke.

3.9.8. Abdominal palpation and auscultation

The normal topographical anatomy and relative position of the abdominal organs are illustrated in Figure 3.3 , Figure 3.4 , Figure 3.5 . Radiography can be used to differentiate abnormalities detected during abdominal palpation. Ultrasound is also useful. Palpation of the abdomen should be done carefully and gently, as it is easy to traumatize the thin-walled viscera.

Topographic view of the abdomen, ventral view. The ventral abdominal wall has been resected to expose the viscera that are illustrated in situ . The diagram was drawn from post-mortem specimens using Barone et al . (1973) as a reference source.

Topographic view of the abdomen, right lateral view. The abdominal viscera are illustrated in situ after resection of the right abdominal wall. The diagram was drawn from post-mortem specimens using Barone et al . (1973) as a reference source.

Topographic view of the abdomen, left lateral view. The abdominal viscera are illustrated in situ after resection of the left abdominal wall. The reproductive tract is not illustrated. The diagram was drawn from post-mortem specimens using Barone et al . (1973) as a reference source.

The spleen is too small to be palpable and the liver is not felt routinely during abdominal palpation. Both kidneys can usually be identified. They are mobile structures. The left kidney lies caudally to the right kidney, which lies close to the rib cage. The stomach cannot be palpated in the normal rabbit. In some cases of gastric stasis, the stomach may be felt as a hard round mass just behind the ribs on the right hand side. Intestinal obstruction causes gross distension of the stomach with gas and liquid (see Box 3.3 ). The caecum may be felt as a soft pliable structure in the ventral abdomen. The size and contents vary with diet and time of day. A full caecum may be felt as a doughy mass. Caecal impactions are felt as a hard sausage-like structure. Gas distension of the caecum can result from gastrointestinal hypomotility. In these cases, the caecum may not be differentiated from other organs or can be felt as a gas-filled structure that makes a sloshing sound when palpated. The bladder can be felt in the caudoventral abdomen. It should be palpated with care as it can rupture easily, especially if the urethra is partially obstructed by a urolith. Rabbits suffering from urolithiasis or cystitis often strain in response to bladder palpation and may void small amounts of urine on to the consulting table.

Gut sounds are not always evident in the healthy rabbit. Absence of gut sounds does not signify intestinal stasis. Tinkling sounds may be heard in distended gas-filled organs such as the caecum or stomach, indicating a gas/fluid interface.

The uterus lies in the ventral abdomen, caudal to the caecum. The broad ligament may contain large quantities of fat that can be seen radiographically. An enlarged uterus due to pregnancy or neoplasia may be felt. Twelve-to-14-day fetuses can be felt as olive-sized masses in the caudal abdomen. As the uterus enlarges it falls forward into the abdomen.

Abdominal masses may be neoplastic. Common neoplasms include uterine adenocarcinoma, lymphomas, liver and kidney tumours. Abdominal abscesses can occur. Areas of fat necrosis may be felt as hard lumps, especially in the remnants of the broad ligament in spayed females.

The limbs, vertebral column and rib cage can be checked for any obvious fractures or deformities.

3.9.9. Auscultation and assessment of respiration

Rabbits have a small rib cage and thoracic cavity. The diaphragm, rather than the intercostal muscles, brings about respiratory movement. Breathing takes place through the nose. Rabbits do not mouth breathe or pant effectively. Respiratory rate varies between 32 and 60 breaths per minute. Increased respiratory rates are indicative of stress, pain, hyperthermia, infection or respiratory disease. Metabolic acidosis can also be manifested by an increased respiratory rate. Upper respiratory tract disease is common in rabbits (see Section 13.2.3). Occlusion of the nasal passage results in increased respiratory effort and may be accompanied by various snuffles, squeaks and whistles. Some short-nosed breeds always make this type of noise. The differentiation between upper and lower airway disease can be made by observation and auscultation and examination of the nose.

An increase in respiratory rate is brought about by an increase in diaphragmatic rather than intercostal movement and can give the impression of dyspnoea. Dyspnoea is manifested by cyanosis, mouth breathing, depression and distress and may or may not be accompanied by an audible respiratory noise. Abnormal, absent or muffled lung sounds may or may not be heard during thoracic auscultation of rabbits with lower respiratory disease. Chronic lung disease cannot be ruled out by auscultation of the chest. Severe lung changes are a frequent incidental finding during post-mortem examination. Abnormal heart sounds can sometimes be detected, although cardiac disease is rare in rabbits in comparison with lung disease. The list of differential diagnoses of dyspnoea is similar to other species.

Normal heart rate varies between 130 and 325 bpm, which is too fast to differentiate heart sounds. Stress increases the heart rate markedly. A pulse can usually be felt in the central artery of the ear ( Figure 3.6 ). A femoral pulse can sometimes be found although it is not as easy to locate in the rabbit as in the dog or cat.

Arteries of the head. The arteries of the cheek may be encountered during surgery on facial abscesses in rabbits. The buccal and lingual arteries are in close proximity with the cheek teeth and can be inadvertently punctured during tooth trimming. The arteries of the ear are also illustrated. A pulse can often be detected by placing a finger on the intermediate ramus of caudal auricular (central) artery of the ear.

Key points 3.6

• • Care should be taken during abdominal palpation as the thin walled viscera are easily traumatized
• • Both kidneys can be felt during routine abdominal palpation
• • The spleen is too small to be palpated
• • The stomach and liver are not usually palpable
• • The caecum may be palpated depending on nature of contents and time of day
• • Palpating the bladder can elicit straining and urination in rabbits with cystitis
• • The uterus cannot be palpated in the non-gravid, healthy animal. During pregnancy it may be felt in the ventral abdomen
• • The thoracic cavity of the rabbit is small
• • Breathing takes place through the nose
• • Respiration is brought about by movement of the diaphragm rather than the intercostal muscles
• • Normal respiratory rate is 32-60 breaths per minute
• • Normal heart rate varies between 130 and 325 bpm
• • A pulse may be felt in the central artery of the ear.

3.9.10. Examination of the face, head and oral cavity

The rabbit can be wrapped in a towel for this part of the examination and held firmly against the body of the owner or nurse.

Visual inspection of the external ear canal may reveal the typical crusty exudate that is associated with Psoroptes cuniculi infestation or the waxy exudate that is often encountered, especially in lop eared breeds. There is a blind ending section of the external ear canal separated by a cartilaginous plate or tragus. Examination of both sides of the tragus can be performed with an auriscope. Auriscopic visualization of the eardrum is difficult due to the length of the auditory canal and the presence of wax and debris.

The skin around the face and head is normally clean and free from debris. Sometimes it is a bonded companion, and not the patient itself, that keeps the head groomed and cleaned. The presence of small scabs in the fur is indicative of a rabbit that is not grooming perhaps due to pain around the face. Saliva staining on the chin or around the mouth is usually indicative of dental disease, although moist dermatitis of deep skin folds under the chin occurs in some loose-skinned breeds. Epiphora causes tear staining and matted fur on the face beneath the medial canthus of the eye, which can lead to superficial pyoderma in that area. Occasionally this is associated with spurs on the upper premolars or molar teeth growing into the mucosa inside the cheek. Grooming the skin over the area becomes painful. The large ears of some lop eared rabbits can sometimes impinge on the eye and surrounding structures causing trauma and irritation.

The head should be palpated and carefully examined for the presence of abscesses on the side of the face, under the masseter muscles or along the bottom of the jaw. One side of the face can be compared with the other. Pain or bony swellings associated with elongated tooth roots can be detected by palpation of the ventral border of the mandible and the zygomatic area (see Section 7.7). The nares should be inspected for signs of a nasal discharge.

The incisors are easily examined by retracting the lips. The molars and premolars can be visualized with the aid of an auriscope or vaginal speculum. With practice, normal and abnormal cheek teeth can be differentiated by this technique, although it is not always possible to determine the cause of an abnormality. Rabbits that resent oral inspection often have problems with their cheek teeth. Excessive saliva, halitosis, presence of food, blood or pus are indicative of dental problems and general anaesthesia is necessary to examine the mouth thoroughly.

3.9.11. Examination of the eyes

Exophthalmos or glaucoma can be seen by comparing the size and shape of the eyes. Fear can cause the eyes to bulge out of the sockets due to engorgement of the orbital vascular sinus (see Figure 3.7 ) ( Eglitis, 1964 ). Retrobulbar abscesses, tumours or cysts can cause a unilateral exophthalmos. The eyelids should be examined for evidence of wounds, ectropion, entropion, meibomian cysts or myxomatosis. The eyes should be clean and free from purulent discharge. The rectus dorsalis muscle can be seen attached to the dorsal sclera when the upper eyelid is retracted. Applying pressure to the area just below the medial canthus of the eye may squeeze pus out of the opening of the nasolacrimal duct in cases with purulent dacrocystitis.

Veins of the head. The veins of the head include the marginal ear vein that is a convenient site for venepuncture. The large orbital venous sinus is also illustrated. This sinus may be encountered during enucleation of the eye and can be a source of serious haemorrhage.

Key points 3.7

• • The tragus is a blind-ending section of the external ear canal separated by a cartilaginous plate
• • Wax and debris often obscure the ear drum especially in lop eared breeds
• • Bilateral exophthalmos can be caused by fear
• • Low Schirmer tear tests are of doubtful significance in rabbits
• • Rabbits produce atropinesterase that can interfere with topical atropine drops used to induce mydriasis.

Nystagmus may be observed by watching the movement of the eye for a few seconds. Occasionally slow nystagmus can be seen in pet rabbits at rest in association with nodding of the head. Affected individuals are usually seropositive for Encephalitozoon cuniculi.

Direct illumination of the eye may reveal pathological conditions of the cornea and uveal tract. Evidence of previous lens rupture and cataract formation is associated with Encephalitozoon cuniculi. Local anaesthesia with topical proxymetacaine drops facilitates examination of the cornea and third eyelid. The application of fluorescein will reveal corneal ulceration. The Schirmer tear test has been evaluated in rabbits. The test paper is inserted into the lower conjunctival fold in the lateral third of the eyelid and is held in place for 1 minute. The amount of wetness is measured in millimetres. Topical anaesthesia is not used. Normal values range from 0 to 11.22 mm/min with a mean of 5.30 + 2.96 having been determined. Low values are of doubtful significance ( Abrams et al ., 1990 ), although absence of tear production can be a sign of dysautonomia. A low Schirmer tear test result indicates keratoconjunctivitis sicca in other species but this condition has not been reported in rabbits. Impaired tear drainage due to nasolacrimal duct disease can result in high Schirmer tear test results, Excessive tear production can also be associated with corneal irritation due to conjunctivitis, corneal abrasions, ulcerations or foreign bodies. Orbital pain may be due to uveitis, glaucoma or retrobulbar disease.

Ophthalmoscopic examination of the fundus and internal structures of the eye requires mydriasis. Rabbits produce atropinesterase, which can interfere with topical atropine eye drops in some individuals. One drop each of 1% atropine and 10% phenylephrine, three to four times during a 15-minute period has been recommended for rabbits ( Kern, 1995 ) or 0.5% or 1% tropicamide can be used. The optic disc lies above the horizontal midline of the eye and it is necessary to look upward into the eye with an ophthalmoscope to view the optic disc which has a deep natural depression (see Section 11.3). The retina is merangiotic (partially vascularized).

3.10. Hospitalization of rabbits

There are many advantages to hospitalizing rabbits. Conditions such as digestive or respiratory tract disorders require close observation and careful nursing. Medication in the form of intravenous fluids, daily injections or nebulization may be necessary. Regular syringe feeding, clipping and bathing may be required. Observation of behaviour, appetite, faecal and urine output is easier if the rabbit is kept on its own under the careful eye of competent nursing staff. A stress-free environment is required, away from barking dogs and the sight and smell of predators along with a good nursing team who understand the nutritional and physiological requirements of rabbits. Hospitalized rabbits should be provided with a bed of good quality hay to nibble and lie on. The familiar smell of hay gives them security. Some rabbits like a cardboard box to hide in. House rabbits can be very particular in their choice of litter material and may be reluctant to use a tray that does not contain the correct type of litter. Most owners are willing to bring in the correct type of material for their rabbit's litter tray. Fresh water needs to be provided in a drinking container that the rabbit is familiar with. Some rabbits will not use a sipper bottle. It is worth considering hospitalizing a bonded companion of a sick rabbit as they can become stressed if they are separated.

3.11. Euthanasia

Euthanasia is defined as ‘an easy or painless death’ ( Blood and Studdert, 1999 ). The traditional approach of an intravenous overdose of barbiturate can be difficult to accomplish easily in rabbits. The marginal ear vein is accessible but many rabbits will jump up suddenly in response to venepuncture, which can be distressing for owner, vet and rabbit. Intraperitoneal barbiturate is acceptable but can take some time for the animal to lose consciousness. Sedation prior to intravenous barbiturate injection is preferable if the owner wishes to be present. The owner may wait with their rabbit until the sedative has taken effect. A combination of acepromazine and butorphanol (0.5 mg/kg acepromazine plus 0.1 mg/kg butorphanol) can be given by subcutaneous injection and has the advantage of vasodilation that facilitates venepuncture. Alternatively, fentanyl/fluanisone (0.3-0.5 ml/kg) (Hypnorm, Janssen) can be used but it is given by intramuscular injection, which is more distressing to patient and owner than a subcutaneous injection. Subcutaneous (50 mg/kg) ketamine with or without other agents can be used. Medetomidine, either on its own or in combination with other agents, is an effective sedative but causes peripheral vasoconstriction, which can make the lethal intravenous barbiturate injection difficult.

3.12. Clinical techniques

3.12.1. chemical restraint.

Chemical restraint is useful for the diagnosis and treatment of many conditions in pet rabbits. It is easier to collect a blood sample or take a well-positioned diagnostic radiograph if the patient is immobile and compliant. Soiled, matted fur or maggots can be removed from sedated rabbits and a period of sedation and analgesia allows time for inflamed skin to respond to treatment. Rabbits with gastrointestinal disease that results in gas-filled viscera such as the caecum or stomach can benefit from a period of analgesia. Intravenous fluid therapy is much easier in a sedated animal.

The properties of sedatives and tranquillizers are described in Section 5.4. Fentanyl/fluanisone (0.2-0.3 ml/kg) (Hypnorm) is a particularly useful for rabbits. Fentanyl/fluanisone is vasodilatory which, in conjunction with its sedative properties, makes venepuncture for the blood sampling or intravenous therapy simple. It is satisfactory method of chemical restraint for radiography, dematting or maggot removal. An alternative to fluanisone/fentanyl is a combination of acepromazine and butorphanol (0.5 mg/kg acepromazine plus 0.1 mg/kg butorphanol). This combination is also sedative and vasodilatory. However, it should be used with care in dehydrated animals or those with cardiovascular disturbances ( Flecknell, 2000 ).

There are many other combinations that can be used as chemical restraint in rabbits, especially in the USA where fentanyl/fluanisone is unavailable ( Mason, 1997 ). Anaesthesia and analgesia are discussed in Chapter 5.

3.12.2. Blood sampling

There are several superficial veins that can be used to collect blood from rabbits. Sites for venepuncture and intraosseous fluid therapy are illustrated in Figure 3.8 . Although laboratory rabbits are sometimes bled by cardiocentesis, this procedure is not suitable for a pet rabbit. Rabbit blood clots extremely fast and has to be collected quickly but in a manner which does not cause haemolysis. Heparinizing the syringe and needle can be advantageous. As a rough guide it is safe to take up to 1% of the animal's bodyweight of blood ( Ramer et al ., 1999 ).

The marginal ear vein is easily visualized and accessible but is too small in some breeds for the blood to flow freely. Blood can be taken quickly from the central ear artery but this procedure carries a small risk of permanent damage to the blood supply to the pinna if the artery is damaged. Part of the pinna may subsequently slough off. Conscious rabbits can jump suddenly and dislodge a needle from an ear vein in response to venepuncture. This response can be avoided by the application of a local anaesthetic cream (EMLA, Astra). EMLA is a mixture of lignocaine and prilocaine that produces anaesthesia of full skin thickness. The cream is applied over the marginal ear vein before covering the site with a dressing or clingfilm. After 45-60 minutes a blood sample can be taken ( Flecknell, 2000 ).

The jugular vein is a satisfactory site for the collection of good quality samples in most rabbits. The dewlap of female rabbits does not pose a problem. It may be difficult to visualize the vessels in obese animals. The rabbit should be wrapped in a towel and held securely by an assistant. The head is extended backwards and the hair over the throat clipped off. The jugular vein can usually be visualized in the jugular furrow and is raised by occluding the vessel by a finger at the thoracic inlet. Up to 10 ml of blood can be safely collected from any sized rabbit from this site. Difficulties can arise with short nosed breeds such as the Netherland Dwarf or animals with upper respiratory tract problems that can become distressed or even cyanosed when the head is extended backwards. Alternative sites such as the cephalic or lateral saphenous veins can be used instead. It is a good idea to make a blood film in addition to placing the blood in sample bottles. The film can be quickly stained and examined for a differential white cell count which, in addition to a PCV, will give an immediate assessment of the rabbit's health status in the absence of sophisticated laboratory equipment. As rabbit blood clots so quickly, heparinized syringes may be required. Analysers such as the I-Stat (Heska) requires heparinized blood but is a useful piece of equipment in the assessment of critically ill rabbits as it can measure parameters such as electrolytes, glucose and urea, using only a few drops of blood.

3.12.3. Urine collection

Urinanalysis is covered in Section 6.5. Urine samples can be collected from house rabbits and from many hutch rabbits by providing a clean but empty litter box placed in the site where the rabbit usually urinates. Cystocentesis is an alternative method of urine collection if the bladder can be easily palpated and differentiated from other structures such as a gravid or neoplastic uterus or an abdominal abscess. Ultrasound can be used to identify the bladder. Repetitive puncture of the bladder can cause inflammation and subsequent stone formation. Rabbits are more prone than other species to developing calculi along a cystotomy suture line ( Kaminski et al ., 1978 ).

Key points 3.8

• • Hospitalization facilitates administration of medication and food and permits observation of demeanour, appetite, thirst, urinary and faecal output
• • A stress-free environment is required for hospitalized rabbits
• • A bedding of hay provides a familiar smell, a sense of security and a source of indigestible fibre
• • Some house rabbits will only use a litter tray containing a familiar substrate
• • Peaceful euthanasia can be accomplished by the administration of 0.5 mg/kg acepromazine + 1.0 mg/kg butorphanol given subcutaneously 10-15 minutes prior to intravenous barbiturate injection
• • Rabbit blood clots quickly. The marginal ear vein can be used for blood collection in large rabbits. The jugular and cephalic veins may also be used
• • Although cystocentesis can be used to collect urine samples, repetitive puncture can cause calculus formation.

Urine can sometimes be collected by manual expression of the bladder, although this procedure is not without risk. The bladder is thin walled and can rupture during manual expression, especially if there is a urethral obstruction. Chronic cystitis causes thickening of the bladder wall making it less susceptible to rupture. Rabbits with cystitis or urolithiasis often urinate in response to palpation of the bladder and void urine that can be collected, if a suitable container is easily available.

3.12.4. Administration of medication

3.12.4.1. subcutaneous injections.

The subcutaneous route is suitable for the administration of most parenteral medications with the exception of some anaesthetic agents. Subcutaneous injections are well tolerated and even owners can inject their rabbit without problems. Occasionally subcutaneous injections of antibiotics or vaccines can result in a skin reaction that may not be noticed until a few days later. These reactions can be minimized by making sure that the needle has penetrated the skin and the medication is injected subdermally rather than intradermally. Massaging the area after giving the injection is also useful. The loose skin over the scruff is the usual subcutane-ous injection site. Subcutaneous fluids (10-20 ml/kg) can be administered either into the scruff or the loose skin over the chest.

3.12.4.2. Intramuscular injections

There are a few products that need to be given intramuscularly to rabbits. Large volumes (> 0.5 ml/kg) should be divided and given in two sites. The cranial muscle mass (quadriceps) of the hind leg is the preferred site. The caudal muscle mass can be used, but the sciatic nerve must be avoided by palpating and identifying the semimembranous, semitendinosus and biceps femoris muscles and ensuring that the injection is given into the muscle. Self-mutilation of the foot has been reported in rabbits as a result of nerve damage during intramuscular injection of ketamine and xylazine into the caudal muscle mass ( Beyers et al ., 1991 ). Tissue damage and muscle necrosis were found at the injection site.

3.12.4.3. Intravenous injections

The usual site for intravenous injection is the marginal ear vein that is accessible and easily visualized in rabbits (see Figure 3.8 ). Rabbits can be restrained by wrapping them in a towel. Topical local anaesthesia with EMLA cream (see Blood sampling) or chemical restraint can be used to prevent head shaking and the needle being dislodged. Small gauge needles, adequate light and good eyesight are required especially in dwarf breeds. An alternative site is the cephalic vein similar to the dog or cat. The rabbit's short legs sometimes make raising the vein difficult. Other veins such as the jugular or femoral veins can be used ( Malley, 1996 ) and the choice is largely a matter of individual preference.

The choice of sites is limited for intravenous catheterization and fluid therapy (see Figure 3.8 ). The femoral or jugular veins are impractical. Usually the marginal ear vein or cephalic vein is used due to the ease of keeping the rabbit in the correct position for intravenous fluids to run once the drip is set up. Intravenous catheters can be held in place with adhesive tape or a few drops of Vetbond or superglue. A simple method is to cut one wing off a 21 g or 23 g butterfly set before placing it in the marginal ear vein. The remaining wing can be superglued to the fur on the pinna to keep the needle in place. No bandaging is required to keep the needle in place in sedated or moribund patients, although a piece of bandage tied around the rabbits neck can be used to hold the giving set out of the way. Most rabbits tolerate the procedure well. Superglue is not as satisfactory for keeping intravenous catheters in place because they have a smaller wing that does not provide a large surface area for the bonding agent.

3.12.4.4. Intraosseous route

This route introduces fluids and drugs into the marrow cavity so they are absorbed into the venous circulation. There are several advantages to this technique which avoids the necessity of cannulating a small collapsed vein in moribund patients. The intraosseous route is often used for small exotic animal patients such as birds, reptiles, guinea pigs and pot-bellied pigs where it is difficult to find a peripheral vein. Most rabbits are large enough and have sufficient accessible veins to use the intravenous route but there are occasions when intraosseous administration of drugs and especially fluids can be life saving. Some practitioners prefer this method of fluid administration and use it routinely. Disadvantages include the risk of introducing infection and causing osteomyelitis. The rate of administration can be slow. These problems can be overcome by using careful aseptic techniques and multiple sites. Immature bones with active growth plates, diseased or fractured bones are not suitable.

A needle is used to bore a hole through a bony prominence into the marrow cavity. Direct penetration of the marrow cavity is easier in the tibia or humerus of the rabbit than the femur. The anatomy of the head of the femur requires penetration of the trochanteric fossa so the cortical bone is penetrated three times instead of once (see Figure 3.8 ). The humerus is the preferred site. In conscious animals, local anaesthetic is infiltrated around the injection site, which is clipped and sterilized prior to the introduction of the needle. A 20-22 gauge needle that is about half the length of the bone is required, i.e. 4-6 cm (1.5-2.5 inches). Spinal needles with a stylet that prevents a plug of bone clogging up the bore are most suitable but ordinary hypodermic needles can be used with a smaller gauge needle or a length of wire acting as the stylet. The bone is penetrated by using the needle as a drill. The needle should be kept straight when boring the hole in the bone. Moving the needle from side to side results in a larger hole than is required and leakage of fluid around the injection site. Penetration of the cortex can be felt as a sudden lack of resistance. The needle may need to be redirected slightly to push it down the medullary cavity. It is important to be certain that the tip of the needle is in the medullary cavity and not pushed against or penetrating the cortex. At this point the stylet is removed and a syringe attached to the needle to aspirate bone marrow which confirms correct placement of the needle. If there is any doubt, radiography is indicated. If the needle is not placed correctly, it should be withdrawn and a different bone selected to attempt the procedure again. Once the needle is placed it can be glued or sutured in place. Dressings and antiseptics can be used for protection and to reduce the likelihood of infection. Heparin should be introduced into the catheter every 4-6 h. The needle should not be left in place for longer than 72 h. When it is removed a light dressing and some antiseptic can be applied to the site ( Anderson, 1995 ).

3.12.4.5. Intraperitoneal route

This route is seldom required for the treatment of pet animals and is more often used in laboratory rabbits. Ideally the bladder should be empty and care is needed to avoid the thin walled caecum that lies in the right ventral abdomen (see Figure 3.3 ). The injection should be given caudal to the umbilicus so there is little chance of penetrating the liver, kidneys or spleen. The inguinal quadrant is the site described by Malley (2000) . It is important to draw back on the syringe to check for intestinal contents, blood or urine in which case the syringe should be withdrawn and another attempt made.

3.12.4.6. Oral administration

There are therapeutic agents that need to be given by the oral route. Medicating the drinking water is unsatisfactory as many preparations flavour the water and make it unpalatable. Adding sucrose to the water has been advocated as a means of overcoming this problem. It is also difficult to ensure the correct dosage when medication is given in the drinking water and there is experimental evidence to show that antibiotics administered by this route are ineffective ( Okerman et al ., 1990 ).

Rabbits can be given tablets, which can be placed in the mouth or administered with a pill giver. Placing tablets in food such as breakfast cereals can be successful and the occasional rabbit will eat tablets voluntarily. Crushing tablets and mixing the powder with honey or baby cereal can also be successful. Powders such as vitamin and mineral supplements can be given with food. Most rabbits will readily accept a piece of bread that has been sprinkled with powder. Liquids can also be given in this way.

Many rabbits are easy to dose with oral liquids. In fact many of them enjoy sweet compounds and will readily accept paediatric syrups or medication mixed with honey or fruit juice such as Ribena. Otherwise the rabbit can be wrapped in a towel and the liquid slowly squirted into the mouth using a syringe inserted in the diastema. Owners can be shown how to do this and most manage well.

3.13. Nutritional support

Nutritional support can be life saving in rabbits. Their metabolism is geared to a constant supply of nutrients from the digestive tract. Anorexia can have dire consequences, especially in fat rabbits as ketoacidosis and hepatic lipidosis can develop rapidly as a result of mobilizing fat reserves. Oral liquids soften and lubricate impacted stomach contents. In the short term, nutritional support is required to provide calories, nutrients, fluids and electrolytes. A readily available source of carbohydrate is required to provide glucose for absorption from the stomach and small intestine and prevent hypoglycaemia and the mobilization of the free fatty acids. In the long term, indigestible fibre and fermentable fibre are required to maintain gut motility and optimal conditions in the caecum for bacterial fermentation. Although fermentable fibre can be administered through a syringe, it is not possible to provide indigestible fibre in this way because it has to be ground down to a fine powder in order to pass through the nozzle. The beneficial effect of long indigestible fibre particles is lost by being ground down to a size smaller than 0.5 mm because particles below this size are moved back into the caecum to undergo bacterial fermentation rather than passing into the colon and stimulating gut motility. Therefore, it is important to encourage sick rabbits to eat as soon as possible. They need a source of palatable indigestible fibre, even if they do not appear to be eating. Hay, grass or dandelions are often the first item to be eaten voluntarily and are often eaten in preference to other foods.

In most instances, nutritional support can be given by syringe feeding three or four times a day. Liquid food (10-20 ml/kg) can be introduced into the mouth through a syringe with or without a small section of tubing attached. Baby foods can be used for this purpose. Cereal based products, pureed fruit or vegetables are palatable and will go through a syringe easily. They are useful in the short term as an immediate source of energy and digestible fibre. Alternatively, extruded rabbit food (SupaRabbit Excel, Burgess) can be moistened and mashed to a paste for syringe feeding, although the fibrous particles tend to block the syringe. The food needs to be ground to a powder to prevent this happening, which detracts from its motility stimulatory properties. Many anorexic rabbits, especially those suffering from dental problems, will eat softened nuggets of extruded food from a dish. Eaten in this way, the food is a source of indigestible fibre.

3.13.1. Nasogastric tubes

Very occasionally a situation can arise where syringe feeding is impossible and it becomes necessary to place a nasogastric tube to provide nutrition. This technique should be used as a last resort because nasogastric tubes stress rabbits and stress reduces gastrointestinal motility and impairs digestive function. An Elizabethan collar is required to prevent a rabbit removing a nasogastric tube and this is not only stress provoking but also prevents caecotrophy. In most cases, syringe feeding is satisfactory and nasogastric tubes can be avoided.

It is easier to place a nasogastric tube in a moribund or anaesthetized rabbit as the nasal mucosa is sensitive and the introduction of a tube can cause sneezing and distress. In the conscious animal, local anaesthetic can be sprayed (Intubeze, Arnolds) or dropped (Opthaine, Ciba) into the nostril. Sufficient time (2-3 minutes) should be allowed to elapse for the anaesthetic to take effect before the tube is introduced. Paediatric tubes (4-8 french) are suitable for this purpose or customized veterinary products are available in varying sizes (Cook Veterinary Products). The tube is measured against the rabbit and marked to give an idea of the position of the tip as the tube is being placed: 3f–4f urinary catheters can be used if a nasogastric tube is not available but holes need to be cut in the side and these can catch on the nasal mucosa as the tube is introduced. To place a nasogastric tube, the rabbit's head is grasped and elevated and the tube introduced into the ventral meatus and directed slightly ventrally (see Figure 3.9 ) The head is then flexed as the tube passes through the nasopharynx into the oesophagus and down into the stomach. Occasionally resistance is encountered in the nasal passage due to an elongated tooth root. In this instance, the other nostril can be tried.

Sagittal section through head. This diagram was drawn from a prepared sagittal section of a rabbit's head using Barone et al . (1973) as a reference source. The structures of the nasal cavity and the position of the ventral meatus can be seen. The larynx is difficult to visualize through the oral cavity because of the large base of the tongue that occupies most of the nasopharynx and obscures the view.

It is possible to pass a nasogastric tube through the larynx and into the trachea and it is important to ensure that the tube is not placed in the trachea before introducing food. Keeping the head flexed minimizes the risk of tracheal intubation. If the tube has been measured up against the patient prior to placement, the length of the tube that has been passed will indicate whether the end is in the trachea or in the oesophagus. Palpation of the oesophagus, listening for breath sounds in the tube or instilling a few drops of water or saline can be helpful to confirm the correct placement of the tube in the stomach. If in doubt, a radiograph can be taken to check the tube's position. The nasal end is secured to the skin of the nose and between the ears using tape butterflies and sutures or superglue. Alternatively it can be secured to the Elizabethan collar, which is required to prevent the rabbit removing or damaging the tube. Nasogastric tubes can be left in place for several days. The rabbit is able to eat with the tube in place.

Complications associated with nasogastric tubes include inadvertent introduction of the tube into the trachea and iatrogenic damage to the mucosa. The nasal mucosa is the primary site for Pasteurella multocida bacteria to reside and trauma to the tissues can stir up infection. Epistaxis can also result from the passage of a nasogastric tube.

3.13.2. Stomach tubes

There are occasions when it is necessary to pass a stomach tube. The most common indication is to decompress the stomach of rabbits with intestinal obstruction. These patients are usually either moribund or sedated. Some clinicians use stomach tubes for nutritional support or to administer medication. The technique carries a risk of inadvertently traumatizing the larynx or passing the tube into the trachea causing breathing difficulties or aspiration pneumonia. It is also possible for the rabbit to chew through the tube and inhale or swallow a section. A gag can be used to prevent the rabbit from chewing the tubing. A piece of wood with a hole drilled through it can be placed in the diastema.

Despite the difficulty of endotracheal intubation in anaesthetized rabbits it is surprisingly easy to pass a stomach tube into the trachea. Selection of a large tube should prevent this happening. The tube can be measured against the animal and an estimate of the length required to reach the stomach. It is then lubricated with a KY jelly before it is passed over the tongue into the oesophagus. After placing the tube, the animal's respiration should be watched for a moment or two and the colour of the mucous membranes checked. A small amount of water can be introduced before giving any medication or food. If in doubt, a radiograph can be taken to check the placement of the tube. In rabbits with gastric dilation, gas and liquid readily pass up and out of the tube as the stomach decompresses.

Approach to the anorexic rabbit. The anorexic rabbit requires prompt diagnosis and appropriate treatment. Chance medication with antibiotic, vitamin or corticosteroid injections is unlikely to be effective and wastes valuable time.

3.13.3. Pharyngotomy and gastrotomy tubes

There are clinical situations where syringe feeding is impossible and a nasogastric tube inadvisable. For example, rabbits with skull injuries or a purulent nasal discharge. A technique for placing a pharyngotomy tube has been described for laboratory rabbits. ( Rogers et al ., 1988 ). Under general anaesthesia a 1 cm incision is made 5 mm from the midline just anterior to the larynx on the left-hand side. A tube is passed through the oral cavity into the oesophagus and down to the stomach. The tube is grasped with artery forceps through the mouth and pushed against the wall of the pharynx to cause a bulge under the skin incision. The muscle overlying the bulge is carefully incised using the hard tip of the artery forceps in the pharynx as a guide. The pharyngeal wall is incised and the oral end of the stomach tube exteriorized through the incision. The tube is then anchored at the pharyngeal incision before being run through the subcutaneous tissues to emerge at the base of the ear where it is anchored with skin sutures. Pharyngotomy tubes placed in this manner have been left in laboratory rabbits for 6-12 months to ensure accurate doses of the drugs that were being tested. The catheters were well tolerated and the rabbits continued to eat and drink without losing weight. This technique could be applied to pet rabbits. Soft feeding tubes designed for oesophagostomy in cats (Cook Veterinary Products) would be suitable for this purpose.

Percutaneous endoscopical gastrotomy (PEG) tubes have been used to administer enteral nutritional support to rabbits ( Smith et al ., 1997 ). This technique does not appear to be as useful in rabbits as it is in dogs and cats. It is difficult to pass an endoscope through the rabbit's mouth and pharynx. In order to have a good endoscopic view, the stomach should be empty which is difficult to achieve in rabbits even if they are prevented from eating caecotrophs. Elizabethan collars or bandages are required to prevent the patient from removing the tube once it is placed and these are not well tolerated.

3.14. Elizabethan collars

Elizabethan collars are used in other species to prevent interference with surgical incisions, wounds, catheters or dressings. There are circumstances when collars need to be fitted to rabbits but there are serious disadvantages. Rabbits fitted with Elizabethan collars can become depressed or even anorexic. The collars are stressful and are most likely to be fitted at a time when it is important to minimize stress levels such as after surgery or during periods of anorexia. Significant elevations in plasma glucose levels have been found in rabbits fitted with collars ( Knudtzon, 1988 ). Elizabethan collars also prevent a rabbit from consuming caecotrophs. Caecotrophs are rich in amino acids and vitamins and necessary for optimum nutrition and wound healing. Good surgical technique, buried subcuticular sutures and the correct choice of suture material reduces the need for Elizabethan collars postoperatively. Alternatively, surgical staples can be used ( Dobbins, 2000 ).

3.15. Nebulization

Nebulization has been described as an adjunct to treatment of upper and lower respiratory tract disease in rabbits ( Callaghan and Raftery, 1998 ). A variety of medications, such as antibiotics, can be mixed with warm saline (38°C) and administered twice a day, via a nebulizer, into the air space of a small cage containing the rabbit. It is important to use isotonic saline as the vehicle. Experimental nebulization of rabbits with hypertonic saline (3.6%) caused extravasation of water into the subepithelial tissue of the airway wall. The formation of oedema was associated with a decrease in compliance and gas exchange ( Hogman et al ., 1997 ).

Key points 3.9

• • Subcutaneous injections are well tolerated by rabbits
• • Intravenous fluids can be given into the marginal ear vein. A butterfly cannula can be superglued to the pinna for easy administration
• • The proximal end of the humerus is the preferred site for intraosseous fluid therapy. The trochanteric fossa at the head of the femur precludes direct penetration of the marrow cavity of the proximal femur
• • Nutritional support is life saving in rabbits and is preferably given by syringe feeding
• • Formulations for nutritional support should include carbohydrate as a source of glucose that can be absorbed from the small intestine to prevent hypoglycaemia and mobilization of free fatty acids
• • Powdered formulations given through a syringe cannot provide indigestible fibre to stimulate gastrointestinal motility. It is long particles of indigestible fibre, not small particles of fermentable fibre that stimulate gut motility
• • Powdered formulations can be a source of fermentable (digestible) fibre as a substrate for caecal microflora
• • A tempting palatable source of indigestible fibre should be available for all sick rabbits. Grass is ideal
• • Elizabethan collars can be stressful and prevent caecotrophy. Nasogastric tubes require the placement of Elizabethan collars and are not necessary for the treatment of most anorexic rabbits.

3.16. Cerebrospinal fluid (CSF) collection and myelography

The increase in status and popularity of rabbits as companion animals has resulted in greater owner expectations of veterinary treatment and there are times when myelography and spinal surgery are required. Cerebrospinal fluid analysis can also be helpful in the differential diagnosis of neurological disease. Cisternal puncture in the rabbit is widely used in laboratory rabbits and the procedure is similar to that for dogs and cats.

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