Investigating the Role of Testosterone Signaling at Androgen Receptors in Resiliency to Social Stress

Social experience can alter how individuals cope with stressful events and contribute to individual differences in stress vulnerability. We have previously tested dominant and subordinate male Syrian hamsters (Mesocricetus auratus) in a conditioned defeat model and found that dominant individuals show reduced defeat-induced changes in behavior compared to subordinates. Dominant hamsters also show increased neural activation following social defeat stress in brain regions that regulate social behavior and coping with stress, including the medial amygdala (MeA). Because winning aggressive encounters generates a surge in plasma testosterone and androgen receptors are abundant in the MeA, we tested whether testosterone signaling at androgen receptors in the MeA contributes to the reduced effects of social defeat stress in dominant hamsters. Our overarching hypothesis was that dominant hamsters experience daily surges in plasma testosterone during the maintenance of their social status that increase the expression of androgen receptors in the MeA, which are necessary for their reduced conditioned defeat response compared to subordinates. We found that dominant hamsters experience a significant rise in plasma testosterone 15-min following an aggressive encounter compared to their pre-encounter baseline, whereas subordinates and control animals showed no change in testosterone. Furthermore, we investigated whether changes in androgen receptor and estrogen alpha-receptor immunoreactivity occur during the maintenance of dominance relationships. We paired male hamsters in daily agonistic encounters for 14 days to establish and maintain dominant/subordinate relationships. Dominant hamsters showed significantly more cells expressing androgen receptor immunoreactivity, but not estrogen alpha-receptor immunoreactivity, in the dorsal MeA (dMeA) and ventral lateral septum (vLS), compared to subordinates and controls. Also, blockade of androgen receptors with flutamide during the maintenance of dominance relationships increased the conditioned defeat response in dominant animals compared to vehicle-treated counterparts. Flutamide-treated dominant animals also showed reduced androgen receptor immunoreactivity in the dMeA, but not the vLS, compared to vehicle-treated dominants. Altogether, these results suggest that the maintenance of dominant social status generates neural plasticity that is associated with an upregulation of androgen receptors in the dMeA, and that activation of androgen receptors is necessary for resistance to conditioned defeat.