Socio-emotional behaviour in a VTAshSHANK3 mouse model of ASD

Social deficits and stereotyped repetitive behaviours are the two core features of autistic spectrum disorders (ASDs) and animal models of these disorders can prove as valuable tools to investigate their mechanisms and causes. Here, we aimed first to better characterize rewarding aspects of social interaction in a three chambers task. Then, we developed a shorter protocol to perform social conditioning place preference (sCPP) and tested the requirement of the conditioning sessions to promote a sCPP by using a group of mice that underwent a trial where the contingencies were not kept between associations of stimuli and chamber. As social interaction can be aversive too, we developed the first protocol of social aversion place preference (sCPA) using an aggressive social stimulus. Finally, we tested the two core domains of ASDs and anxiety that is often comorbid in these disorders in a mouse model (shShank3) in which SHANK3 was downregulated specifically in the ventral tegmental area (VTA) that plays a key role in social motivation. Even thought a bidirectional social interaction is not required to promote a social preference it seems to be crucial to sustain and improve a reciprocal motivation, which will facilitate a stable long-term relationship. Our sCPP and sCPA protocols showed the relevance of the conditioning sessions and are time sparing. ShShank3 mice displayed social interaction deficits and repetitive behaviour but did not show any increased anxiety compared with controls