Role of 5-HT1A-AR overexpression in affective disorders

描述（由申请人提供）：重度抑郁症是一种常见的精神疾病，部分原因是血清素（5-HT）神经传递减少。最近的证据表明，这种减少可能是由于5-HT神经元上抑制性5-HT1A自受体（5-HT1A- ar）的表达增加所致。为了模拟抑郁症病理生理的这一方面，我创造了转基因小鼠，设计使其过度表达5-HT1A-AR；我推测这些老鼠会减少5-羟色胺的传播和抑郁样行为。目的1：通过定量放射自显影和免疫细胞化学验证5-HT1A-AR在转基因小鼠中的过表达。目的2：通过体内微透析和电生理检测5-HT1A-AR过表达对5-HT神经传递的影响。目的3：确定5-HT1A-AR过表达对神经植物功能和抑郁样行为的影响。这些研究应该增加我们对抑郁症和其他情感障碍的潜在原因的理解，并可能为患有这些疾病的患者带来新的治疗策略。

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.