Oxytocin and 'social hyperthermia': Interaction with β₃-adrenergic receptor-mediated thermogenesis and significance for the expression of social behavior in male and female mice

Oxytocin (OT) is a critical regulator of multiple facets of energy homeostasis, including brown adipose tissue (BAT) thermogenesis. Nevertheless, it is unclear what, if any, consequence the thermoregulatory and metabolic effects of OT have for the display of social behavior in adult rodents. Here, we examine the contribution of the OT receptor (OTR) and β₃ adrenergic receptor (β₃AR) to the increase in body temperature that typically accompanies social interaction (i.e., social hyperthermia; SH) and whether SH relates to the expression of social behavior in adult mice. Specifically, we examined how OTR antagonism via peripheral injection of L-368,899 (10 mg/kg) affects the expression of social behavior in C57BL/6J mice, in the presence of active/agonized versus antagonized β₃AR, the receptor known to mediate stress-induced BAT thermogenesis. After drug treatment and a 30 min delay, mice were provided a 10 min social interaction test with an unfamiliar, same-sex conspecific. We hypothesized that OTR and β₃AR/BAT interact to influence behavior during social interaction, with at least some effects of OT on social behavior dependent upon OT's thermal effects via β₃AR/BAT. We found that OTR-mediated temperature elevation is largely responsible for SH during social interaction in mice-albeit not substantially via β₃AR-dependent BAT thermogenesis. Further, our results reveal a complex relationship between OTR, β₃AR, social hyperthermia and the display of specific social behaviors, with SH most closely associated with anxiety and/or vigilance-related behaviors-that is, behaviors that antagonize or interfere with the initiation of close, non-agonistic social behavior.