Neuroendocrine mechanisms contributing to individual differences and experience-dependent plasticity in stress-related behavior

Abstract

Stress is a contributing factor in the etiology of several mood and anxiety disorders, and animal models of social defeat have been used to investigate the biological basis of stress-related psychopathologies. Syrian hamsters are highly aggressive and territorial, but after social defeat they exhibit a conditioned defeat (CD) response which is characterized by increased submissive behavior and a failure to defend their home territory against a smaller, non-aggressive intruder. We have previously shown that obtaining a dominance status in male hamsters will contribute to a reduced conditioned defeat response compared to subordinate counterparts. We have also shown that dominant males obtain greater androgen receptor (AR) expression and display greater expression of c-Fos+ cells in the posterior medial amygdala (MeP) after social defeat exposure compared to subordinates. Together, this suggests that the development of a dominance status contributes to neuroplasticity in the MeP including neuroendocrine mechanisms such as AR that contribute to the resistance of social defeat stress. The overall goal of the research projects in this dissertation was to discover neuroendocrine mechanisms that contribute to experience-dependent changes in stress-related behavior. The overarching hypothesis that distinct neuroendocrine mechanisms in the MeP contributes to changes in stress vulnerability in dominant and subordinate hamsters. Chapter 1 provides an overview of the current literature with aims for the research conducted. Chapter 2 investigated whether male and female hamsters differ in their patterns of agonistic behavior during the formation and maintenance of dominance relationships. Chapter 3 investigated whether AR+ cells in the MeP are activated during social defeat stress or testing for anxiety-like behavior in dominant and subordinate male hamsters. Chapter 4 aimed to determine whether activation of MeP and medial prefrontal cortex (mPFC) neurons are associated with female status-dependent differences in resistance to social defeat stress and defeat-induced loss of social motivation. Chapter 5 tested whether AR expression in BNST-projecting MeP cells is essential for resistance to social defeat stress in dominant males. Collectively, these projects delineate neuroendocrine mechanisms by which dominance status influences stress-related behavior