SEROTONIN 1B AND 1A RECEPTORS AND SSRI ANTIDEPRESSANTS

血清素 1B 和 1A 受体以及 SSRI 抗抑郁药

• 批准号: 6185261
• 负责人: CORNELIUS T GROSS
• 金额: $ 3.75万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-15 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6185261
• 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）：该研究建议涉及抗抑郁药的作用机理。具体而言，它试图确定在特定组织中是否需要5HT1B和5HT1A受体，以实现选择性5-羟色胺再摄取抑制剂（SSRIS）的抗抑郁作用。在第一个目标中，我们将扩展以前的实验，显示了SSRIS在强制游泳测试中的抗抑郁作用中对5HT1B受体的要求，这是行为绝望的测试。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中的测定中的作用。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功能的应力保护测定中的作用。在最终目的中，我们将尝试定义这些受体在慢性SSRI功能测试中的作用，慢性SSRI功能是一种抗抑郁作用的模型，更紧密地模仿它们在人类中的功能。