Role of 5-HT1A-AR overexpression in affective disorders

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DESCRIPTION (provided by applicant): Major depression is a common mental illness thought to arise in part from decreased serotonin (5-HT) neurotransmission. Recent evidence suggests that this decrease may arise from increased expression of inhibitory 5-HT1A autoreceptors (5-HT1A-AR) on 5-HT neurons. To model this aspect of the pathophysiology of depression, I have created transgenic mice designed to overexpress 5-HT1A-AR; I hypothesize that these mice will have decreased 5-HT transmission and depressive-like behavior. Aim 1: Validate 5-HT1A-AR overexpression in transgenic mice by quantitative autoradiography and immunocytochemistry. Aim 2: Determine the effect of 5-HT1A-AR overexpression on 5-HT neurotransmission by in vivo microdialysis and electrophysiology. Aim 3: Determine the effect of 5-HT1A-AR overexpression in tests of neurovegetative function and depressive-like behavior. These studies should increase our understanding of the underlying causes of depression and other affective disorders, and may lead to new treatment strategies for patients suffering from these disorders.