Stress triggers not only an immediate response from specialized stress response systems, but triggers adaptive processes that are manifest by an altered magnitude of subsequent stress responses. Thus, exposure to repeated stress often leads to either habituation or sensitization of stress responses. Although substantial progress has been made in understanding the immediate physiological response to stress, as well as some of the physiological consequences of repeated stress, very little progress has been made in understanding the adaptive processes that contribute to stress response habituation or sensitization. These adaptive processes, however, may be crucial in determining the long-term physiological and psychological consequences of stress. Some psychological disorders may be directly, related to the development of sensitized stress responses (e.g. post- traumatic stress disorder) or to the impaired development of stress response habituation (e.g. depression). Previous studies have found in rats that the expression of hypothalamic-pituitary- adrenal (HPA) axis stress-response habituation is dependent on corticosteroid hormone activity in the brain mediated by mineralocorticoid receptors (MR). The proposed project will further study mechanisms by which corticosterone regulates stress habituation. The specific aims are: (1) to determine the anatomical site(s) responsible for MR antagonist modulation of HPA axis stress habituation, (2) to determine whether the expression of HPA axis stress habituation and its blockade by MR antagonist treatment is associated with changes in corticotropin releasing hormone (CRH) and arginine vasopressin (AVP) gene expression in the paraventricular nucleus of the hypothalamus (PVH), (3) to determine whether HPA axis stress habituation is associated with a generalized shift in HPA axis dependence on MR- media corticosteroid negative feedback, and (4) to determine whether HPA axis stress habituation is associated with a change in MR or glucocorticoid receptor (GR) expression in the rat brain.

R01MH062456

2001-07-01

2006-12-31