Affiliations: Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Site, Cambridge, UK
Note:  Correspondence to: Professor A. Jenny Morton, Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Site, Cambridge CB2 3DY, UK. Tel.: +44 1223 334057; E-mail: [email protected]
Abstract: Background: Huntington's disease (HD) is characterised by a combination of motor, cognitive and psychiatric symptoms. HD patients also exhibit deficits in social behaviour. While motor and cognitive dysfunction in the R6/2 transgenic mouse model of HD has been well described, social disorders have not been reported. Objective: To compare social behaviour in R6/2 and wildtype (WT) mice, using two different measures of sociability. Methods: R6/2 mice were tested in the habituation/dishabituation test as a measure of social recognition, and the resident-intruder paradigm, as a measure of social interaction. Results: In the social recognition test, WT mice remained interested in female mice throughout the testing period. Male R6/2 mice showed reduced interest in female mice from 14 weeks of age, while still recognising novel female mice. In the resident-intruder test, R6/2 residents showed a lack of interest in the intruder. Interestingly, WT resident mice showed more aggressive behaviour towards R6/2 than WT intruders. This aggressive behaviour stopped once the barrier was removed, but WT mice showed increased risk assessment and escape behaviours while interacting with R6/2 intruders. Conclusions: R6/2 mice have deficits in social behaviours. Phenotypic male R6/2 mice show a decreased interest in females, mirroring the hyposexuality seen in HD patients. Furthermore, R6/2 mice show a lack of interest in intruder mice, suggesting social apathy. The abnormal response of WT mice to R6/2 mice suggests that R6/2 mice do not generate appropriate social cues. Our data suggest that R6/2 mice have deficits in social behaviour that replicate the disrupted social behaviours seen in HD.
Keywords: Huntington's disease, social interaction, resident-intruder, transgenic mouse