# Adolescent social instability stress alters social processes in male prairie voles

## TL;DR

Stress during adolescence in male prairie voles changes how they interact socially and respond to stress in adulthood.

## Contribution

This study reveals how adolescent social instability stress reorganizes social reward circuits without suppressing social behavior.

## Key findings

- SIS subjects showed reduced affiliative contact and increased social investigation during adolescence.
- SIS subjects consistently displayed a stress-resilient phenotype compared to more variable CTL subjects.
- Correlation analyses revealed disrupted oxytocin-dopamine receptor coupling in SIS subjects.

## Abstract

Adolescence is a sensitive period for the maturation of neural circuits governing goal-directed social behaviors and stress regulation. Disruption of stable social relationships during adolescence can alter neuropeptide and dopaminergic systems that shape adult social behaviors. We investigated the behavioral and neurobiological consequences of adolescent social instability stress (SIS) in male prairie voles (Microtus ochrogaster), a species that forms selective social bonds between peers, mating partners, and parents and their offspring. During adolescence, SIS subjects experienced repeated reshuffling of cage mates to disrupt stable peer bonds, while control (CTL) subjects remained in fixed pairs. Home cage observations after and right before each reshuffling revealed that SIS subjects exhibited reduced affiliative contact and sustained social investigation compared to CTL subjects, despite no group differences in body weight throughout adolescence. Moreover, SIS and CTL groups did not differ in social zone duration or latency to approach a novel conspecific during the social approach test (SAT). Stress phenotypes were classified by assessing the duration of social zone occupancy during the SAT under baseline and stimulus-present conditions. Remarkably, all SIS subjects expressed a consistent stress resilient phenotype in contrast to CTL subjects whose responses were more variable, spanning both stress resilient and susceptible phenotypes. Gene receptor expression analyses revealed no group differences in oxytocin (Oxtr), arginine vasopressin (Avpr1a), and dopamine (Drd1 and Drd2) gene expression within the lateral septum (LS), nucleus accumbens (NAc), or anterior cingulate cortex (ACC), brain regions important for modulating goal-directed social behaviors and stress responses. However, correlation analyses indicated distinct relationships between gene receptor expression and social behaviors across groups, including a negative association between LS- Avpr1a expression and the latency to approach a novel conspecific in only CTL subjects. Additionally, associations between ACC-Drd2 expression and the latency to approach a stimulus were in opposing directions between groups. Correlation analyses solely between gene receptor expression revealed the loss of oxytocin-dopamine receptor coupling in the LS and ACC of SIS but not CTL subjects. Together, these findings suggest that adolescent SIS does not globally suppress social behavior but instead may reorganize social reward circuitry to promote behavioral flexibility and stress resilience.