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The UFAW 3Rs Liaison Group Research Studentship

Claire Richardson, Newcastle University

Refining research procedures by assessing distress in laboratory rodents

In 2007 Claire Richardson was awarded a 3Rs Liaison Group Studentship to develop methods to improve objective methods of assessing the welfare and emotional state of laboratory mice, the most commonly used laboratory animal. Ms Richardson undertook her project at Newcastle University under the supervision of Professor Paul Flecknell.

Determining the affective state of animals, or how they ‘feel’, is essential if we are to make meaningful judgements about their welfare and to assess the value of measures aimed at improving their welfare. Emotional states such as fear and anxiety are typically assessed in laboratory rodents by measuring the responses of individual animals in standardized behavioural tests, such as the elevated plus maze. Although these tests are widely used, individual testing of animals can be stressful and repeated testing of the same animal can be problematic and time consuming.

Claire was interested in investigating how mouse behaviour could be measured through using non-invasive automated technology, in particular Claire focused on the Intellicage® - a transponder-based automated home-cage that can collect and record certain behavioural data (e.g. activity levels, nosepokes, drinking). The capacity to non-invasively study rodents in a social setting would have scientific, animal welfare and economic advantages.

Claire undertook a series of three experiments: 1) developing a task to examine cognitive biases in an automated homecage, 2) examining measures from the automated homecage that may relate to standardised measures of well-being, and 3) studying analgesic (pain-relief) seeking behaviour in mice with cancer.

During the first series of experiments, anxiety-like behaviour from 32 individual mice from two commonly used strains of inbred wild-type laboratory mice was assessed using standardized behavioural tests. The same animals were then examined whilst group-housed using a novel assessment technique: response to unpredictable, mild airpuffs in an automated homecage. Claire found that individual mouse behaviour in the emergence test was positively correlated with individual response to airpuffs, e.g. individuals with the greatest latency to leave a shelter in the emergence test showed the greatest response to airpuffs. The findings of this study suggest that examining reactivity to unpredictable, mild airpuffs may be a useful technique to non-invasively assess fear and anxiety in socially housed animals.

In the second series of experiments mice with three types of cancer (bladder, subcutaneous and intramuscular) were studied in the automated homecage. Although mice are frequently used as models in cancer research, relatively little is known about which studies are painful and when pain/distress is most likely to occur. Subtle behavioural changes detected by the homecage preceded clinical signs of disease in mice with bladder and intramuscular cancer. These findings have implications for the implementation of humane endpoints in cancer research. If exploratory changes in behaviour reliably precede clinical disease it may be possible to humanely kill animals prior to the onset of pain or distress without compromising the scientific outcomes of many studies.

With the aim of developing methods for the objective assessment of cancer pain, in addition to examining the spontaneous behaviour of mice with cancer within in automated homecage, analgesic self-administration and place preference were also studied. This work provided evidence that quickly developing tumours were likely to be associated with acutely painful periods. Mice with quickly developing tumours were significantly more likely to approach a homecage location associated with morphine compared to control animals. The strength of the animals with cancer peak preference for the morphine location was also positively correlated with the speed of the tumour growth.

Claire concluded that this project provided evidence of a variety of ways in which an automated system can be used to monitor the welfare of laboratory mice. A further advantage is that this intensive monitoring takes place non-invasively in socially housed animals within enriched homecages.

Dr Richardson was awarded her PhD in 2012

Published papers arising from Claire’s work supported by UFAW:

Richardson CA. 2015. The power of automated behavioural homecage technologies in characterizing disease progression in laboratory mice: A review. Applied Animal Behaviour Science. 163: 19-27. https://doi.org/10.1016/j.applanim.2014.11.018.

Coulter CA, Flecknell PA, Leach MC, Richardson CA. 2011. Reported analgesic administration to rabbits undergoing experimental surgical procedures. BMC Veterinary Research. 7: 12. DOI: 10.1186/1746-6148-7-12.

Miller AL, Richardson CA. 2011. Rodent Analgesia. Veterinary Clinics of North America: Exotic Animal Practice, Analgesia and Pain Management. 14(1): 81-92. https://doi.org/10.1016/j.cvex.2010.09.004.

Leach MC, Coulter CA, Richardson CA, Flecknell PA. 2011. Are We Looking in the Wrong Place? Implications for Behavioural-Based Pain Assessment in Rabbits (Oryctolagus cuniculi) and Beyond? PLoS ONE 6(3): e13347. https://doi.org/10.1371/journal.pone.0013347

Coulter CA, Flecknell PA, Richardson CA. 2009. Reported analgesic administration to rabbits, pigs, sheep, dogs and non-human primates undergoing experimental surgical procedures. Laboratory Animals. 43(3): 232-238. DOI: https://doi.org/10.1258/la.2008.008021.

Stokes EL, Flecknell PA, Richardson CA. 2009. Reported analgesic and anaesthetic administration to rodents undergoing experimental surgical procedures. Laboratory Animals. 43(2): 149-154.  doi: 10.1258/la.2008.008020.

Leach MC, Allweiler S, Richardson C, Roughan JV, Narbe R, Flecknell PA. 2009. Behavioural effects of ovariohysterectomy and oral administration of meloxicam in laboratory housed rabbits. Research in Veterinary Science. 87(2): 336-347. DOI: 10.1016/j.rvsc.2009.02.001