Large nesting in deer mice co-occurs with jumping but not running stereotypies: Insights into compulsive-like...

Subpopulations of deer mice present with distinct compulsive-like behavioural phenotypes, i.e., large nesting (large nest-building [LNB]) and high motor stereotypy (HS). Large nest-building and HS associate with unique dopaminergic and adenosinergic mechanisms. Large nest-building is also characterized by increased risk-taking behaviour, which has not yet been shown in HS mice. We hypothesised that LNB and HS represent distinct compulsive-like outcomes that would not manifest in the same subjects. We also hypothesised that LNB and HS would each respond uniquely to dopamine D₁ receptor modulation, confirming distinct neurobiological profiles that could guide future studies aimed at enhancing treatment outcomes. Briefly, 267 mice were screened for nesting behaviour, of which 36 mice were selected for normal nesting (normal nest-building [NNB]) and 44 for LNB. Mice were subsequently exposed to either control injections or to the highly selective D₁ agonist (SKF-38393), D₁ antagonist (ecopipam), or the A₁ agonist (capadenoson) for 32 days. Mice were then retested for nesting and stereotypy expression and risk-prone open field behaviour. We show that LNB is associated with lower overall motor stereotypical expression compared with NNB. We also show that vertical jumping co-occurs with both NNB and LNB behaviour, whereas pattern running is only shown by NNB mice and that neither LNB nor HS was impacted by selective D₁ receptor modulation. Collectively, these results strengthen earlier observations in deer mice with respect to compulsive-like behavioural heterogeneity and provide a solid foundation for research into the aetiology of equally persistent and repetitive but unique compulsive-like behavioural phenotypes.