Project Summary Social stress is a risk factor for several stress-related psychopathologies, including post-traumatic stress disorder (PTSD). However, most individuals exposed to trauma do not develop stress-related psychopathologies and previous social experience has the potential to improve coping strategies and enable stress resilience. One social experience that contributes to the development of stress resilience is a dominant position in a social hierarchy. In this proposal, we use a Syrian hamster model in which dominant animals show less stress-related behavior than their subordinate counterparts. Our preliminary data indicate that male dominants show increased c-Fos immunoreactivity in androgen receptor (AR)-positive cells in dorsal aspects of the posterior medial amygdala (MePD) compared to their subordinate counterparts. In addition, they show increased c-Fos immunoreactivity in MePD cells projecting to posterior regions of the bed nucleus of the stria terminalis (BNSTp) compared to subordinates. Unlike males, dominant female hamsters have a greater number of estrogen receptor alpha (ERα)-positive cells in the MePD compared to subordinates. However, dominant females do not show elevated c-Fos immunoreactivity in BNSTp-projecting MePD cells compared to subordinates. Altogether, these findings suggest that while AR expression in a MePD-BNSTp pathway may be critical for status-dependent differences in stress vulnerability in male hamsters, ERα expression in MePD- BNSTp pathway may not contribute to status-dependent differences in stress vulnerability in female hamsters. Because of these sex differences, we have two separate hypotheses in this proposal. We hypothesize that AR+ neurons in a MePD-BNSTp pathway are essential for status-dependent differences in stress-related behavior in male hamsters. Also, we hypothesize that ERα+ cells in the MePD are necessary for status- dependent differences in stress-related behavior in female hamsters. We will use a Cre-dependent AAV vector that expresses a short hairpin RNA (shRNA) for AR to selectively knockdown AR receptors in a MePD-BNSTp pathway. In addition, we will use an AAV-shRNA to knockdown ERα receptors in the MePD in a non-Cre- dependent manner in both females and males. Overall, this project will investigate the cellular mechanisms and neural circuits by which gonadal steroid hormone receptors contribute to status-dependent changes in stress vulnerability. This line of research will determine how social experience generates neural plasticity in select neural ensembles and thereby changes stress vulnerability in a sex-dependent manner.

Project Narrative Traumatic stress is a risk factor for several stress-related psychopathologies. This proposal used a rodent model to investigate the neuroendocrine mechanisms by which social experience changes neural circuits and reduces stress vulnerability. This line of research will aid in the development of interventions that enhance coping strategies and promote stress resilience.