Amygdala GR Function in Stress Activation and Promotion

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DESCRIPTION (provided by applicant): Depression, a destructive psychiatric disorder, is estimated to affect 18 million people per year. Anxiety and memory changes associated with depression have been connected to a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, the endocrine stress response. HPA axis and behavioral changes can be either positive (i.e., increasing HPA drive and behavior) or negative (i.e., decreasing drive) in a state of chronic stress. It has been postulated that the various effects of stress on anxiety and memory can be at least partially accounted for by the altered activity of glucocorticoid receptors (GR). In accord with this hypothesis, evidence from pharmacological and genetic studies has demonstrated the capacity of differing amounts of GR activity in different brain areas to produce contrasting changes on anxiety and memory. Specifically, GRs in the hippocampus and hypothalamus are involved in decreasing HPA axis drive while GR in the amygdala is thought to be involved in increasing drive and anxiety. To determine the role of amygdalar GR in depression-related changes and HPA axis modulation, current gene therapy and knockout technology will be used to produce mice with amygdalar disruption of GR.