Sex-dependent effects of adolescent chronic social defeat and social accompanying on emotional and social behaviors and the numbers of OT/Fos and AVP/Fos dual-labelled cells in brain regions of the mandarin vole (Microtus mandarinus).

Abstract

This study investigated the effects of chronic social defeat stress (CSDS) on depression-like behaviors in adolescent male and female Mandarin voles (Microtus mandarinus). Additionally, we examined the role of social accompanying during CSDS in mitigating CSDS-induced changes in depression-like behaviors, as well as activities of oxytocin (OT) and 17 arginine vasopressin (AVP) neurons. CSDS exposure reduced sucrose preference and social interaction in both sexes. However, CSDS increased immobility time in the tail suspension test (TST) and forced swim test (FST) only in females. Social accompanying increased sucrose preference and social interaction in both sexes, while reducing immobility time in the TST and FST exclusively in females. These results suggest that social accompanying may enhance stress resilience in adolescent voles of both sexes, particularly in females. At the neural level, CSDS led to a decrease in OT/c-Fos-positive cells in the paraventricular nucleus (PVN), supraoptic nucleus (SON), bed nucleus of the stria terminalis (BNST), and medial amygdala (MeA) in females, but increased activation in these regions in males. Social accompanying reversed these changes in females, but not in males, indicating a stronger accompanying effect of social interaction on OT neuron activity in females. Conversely, CSDS decreased AVP/c-Fos-positive cells in the PVN, SON, BNST, and MeA in males, suggesting greater AVP involvement in the male stress response. Social accompanying reversed these AVP-related changes in males, but not in females. These findings highlight sex-dependent neural and behavioral responses to CSDS and identify potential mechanisms through which social interaction promotes stress resilience during adolescence. OT and AVP activity in the PVN, SON, BNST, and MeA may serve as molecular substrates for the protective effects of social accompanying, shaping both behavioral and neural outcomes.