Androgen receptors in a neural circuit from the medial amygdala to the bed nucleus of the stria terminalis regulate responses to social challenges.

Androgen receptor (AR) signaling in the posterior medial amygdala (MeP) plays a critical role in promoting resistance to social defeat stress in dominant male Syrian hamsters. The MeP is densely interconnected with the bed nucleus of the stria terminalis (BNST), and the MeP-BNST pathway is essential for regulating aggression and responses to social threats. Here, we tested the hypothesis that AR signaling within MeP-BNST projection neurons is required for stress resistance in dominant animals. We first used a short hairpin RNA (shRNA) virus to reduce AR expression in MeP neurons. Male and female Syrian hamsters were then exposed to acute social defeat stress and assessed for stress-related behavior using conditioned defeat and social avoidance tests. In a separate experiment, male hamsters established dominance relationships prior to acute social defeat exposure and testing for stress-related behavior. Dominant males with AR knockdown in MeP-BNST neurons displayed increased territorial aggression before social defeat and greater submissive and defensive behavior following defeat. They also exhibited increased social investigation prior to social defeat. Together, these findings demonstrate that AR signaling within the MeP-BNST pathway is required for stress resistance in dominant males and contributes to the inhibitory control of social investigation and aggression. In contrast, AR knockdown in MeP neurons did not alter social avoidance or agonistic behavior in female hamsters, highlighting a pronounced sex difference. Overall, these findings demonstrate that androgen signaling within a discrete MeP-BNST circuit regulates behavioral responses to social threats in dominant male hamsters and delineate a neuroendocrine mechanism underlying stress resistance.