SEROTONIN 1BAND1A RECEPTORS AND SSRI ANTIDEPRESSANT

血清素 1BAND1A 受体和 SSRI 抗抑郁药

• 批准号: 2863018
• 负责人: CORNELIUS T GROSS
• 金额: $ 3.17万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-15 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2863018
• 关键词: antidepressants; basal ganglia; behavior test; fluoxetine; gene targeting; genetically modified animals; hippocampus; laboratory mouse; neuropharmacology; paroxetine; receptor expression; serotonin inhibitor; serotonin receptor; stress

DESCRIPTION (Applicant's abstract): This research proposal addresses the mechanism of action of antidepressants. Specifically, it seeks to determine whether the 5HT1B and 5HT1A receptors are required in specific tissues for the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs). In the first aim, we will extend previous experiments showing a requirement for 5HT1B receptors in the antidepressant effects of SSRIs in the forced swim test, a test of behavioral despair. We will use tissue specific knockouts of the mouse 5HT1B and 5HT1A receptors to test their role in this assay in the basal ganglia and hippocampus. In the second aim, we will use similar methods to investigate the role of 5HT1B and 5HT1A receptors in a stress protective assay of SSRI function. In the final aim, we will attempt to define the role of these receptors in a test of chronic SSRI function, a model of antidepressant action more closely mimicking their function in humans.

描述（申请人的摘要）：本研究提案涉及抗抑郁药的作用机制。具体来说，它试图确定特定组织中是否需要 5HT1B 和 5HT1A 受体来发挥选择性血清素再摄取抑制剂 (SSRI) 的抗抑郁作用。第一个目标是，我们将扩展之前的实验，证明在强迫游泳测试（一项行为绝望测试）中，SSRI 的抗抑郁作用需要 5HT1B 受体。我们将使用小鼠 5HT1B 和 5HT1A 受体的组织特异性敲除来测试它们在基底神经节和海马体测定中的作用。在第二个目标中，我们将使用类似的方法来研究 5HT1B 和 5HT1A 受体在 SSRI 功能的应激保护测定中的作用。在最终目标中，我们将尝试定义这些受体在慢性 SSRI 功能测试中的作用，这是一种更接近地模拟它们在人类中的功能的抗抑郁作用模型。