Gonadal steroid hormone receptors in the medial amygdala contribute to experience-dependent changes in stress vulnerability.

Social experience can generate neural plasticity that changes how individuals respond to stress. Winning aggressive encounters alters how animals respond to future challenges and leads to increased plasma testosterone concentrations and androgen receptor (AR) expression in the social behavior neural network. In this project, our aim was to identify neuroendocrine mechanisms that account for changes in stress-related behavior following the establishment of dominance relationships over a two-week period. We used a Syrian hamster model in which acute social defeat stress increases anxiety-like responses in a conditioned defeat test in males and in a social avoidance test in females. First, we administered flutamide, an AR antagonist, via intraperitoneal injections daily during the establishment of dominance relationships in male hamsters. We found that pharmacological blockade of AR prevented a reduction in conditioned defeat in dominant males and blocked an upregulation of AR in the posterior dorsal medial amygdala (MePD) and posterior ventral medial amygdala (MePV), but not in the ventral lateral septum. Next, we administered flutamide into the posterior aspects of the medial amygdala (MeP) prior to acute social defeat stress or prior to conditioned defeat testing in males. We found that pharmacological blockade of AR in the MeP prior to social defeat, but not prior to testing, increased the conditioned defeat response in dominant males and did not alter behavior in subordinates. Finally, we developed a procedure to establish dominance relationships in female hamsters and investigated status-dependent changes in plasma steroid hormone concentrations, estrogen receptor alpha (ERα) immunoreactivity, and defeat-induced social avoidance. We found that dominant female hamsters showed reduced social avoidance regardless of social defeat exposure as well as increased ERα expression in the MePD, but no status-dependent changes in the concentration of plasma steroid hormones. Overall, these findings suggest that achieving and maintaining stable social dominance leads to sex-specific neural plasticity in the MeP that underlies status-dependent changes in stress vulnerability.

Winning agonistic encounters increases testosterone and androgen receptor expression in Syrian hamsters.

Winning aggressive disputes is one of several experiences that can alter responses to future stressful events. We have previously tested dominant and subordinate male Syrian hamsters in a conditioned defeat model and found that dominant individuals show less change in behavior following social defeat stress compared to subordinates and controls, indicating a reduced conditioned defeat response. Resistance to the effects of social defeat in dominants is experience-dependent and requires the maintenance of dominance relationships for 14days. For this study we investigated whether winning aggressive interactions increases plasma testosterone and whether repeatedly winning increases androgen receptor expression. First, male hamsters were paired in daily 10-min aggressive encounters and blood samples were collected immediately before and 15min and 30min after the formation of dominance relationships. Dominants showed an increase in plasma testosterone at 15min post-interaction compared to their pre-interaction baseline, whereas subordinates and controls showed no change in plasma testosterone. Secondly, we investigated whether 14days of dominant social status increased androgen or estrogen alpha-receptor immunoreactivity in brain regions that regulate the conditioned defeat response. Dominants showed more androgen, but not estrogen alpha, receptor immuno-positive cells in the dorsal medial amygdala (dMeA) and ventral lateral septum (vLS) compared to subordinates and controls. Finally, we showed that one day of dominant social status was insufficient to increase androgen receptor immunoreactivity compared to subordinates. These results suggest that elevated testosterone signaling at androgen receptors in the dMeA and vLS might contribute to the reduced conditioned defeat response exhibited by dominant hamsters.