5-HT-1A RECEPTOR ADAPTATIONS IN ANTIDEPRESSANT RESPONSE

该项目建立在研究者以前对多巴胺能神经递质的研究基础上。 抗抑郁药应答者之间的差异 vs.那些没有回应的。 这项研究建议将数据从 PI的实验室迄今表明，慢性，但不是急性，5-HT 1A 部分激动剂给药可能具有抗抑郁作用， 使抑郁症患者的人5-HT 1A受体刺激反应脱敏 患者 该提案旨在检验标准 抗抑郁治疗与5-HT 1A受体介导的 适应性，将区分治疗反应， 去甲替林 该项目采用标准的去甲替林治疗方案， 由研究者检测 抗抑郁药应答者与抗抑郁药无应答者。 的 到目前为止，去甲替林治疗设计已成功用于测试 治疗期间不同时间点的反应组， 足以检验生物学差异的不同缓解队列 在群体之间。 本研究基于研究者的IND#，使用5-HT 1A 在设计用于测试 5-HT 1A预处理和 突触后受体亚型，在一个新的方法，旨在探索 5-HT 1A受体适应可能是 对标准抗抑郁药治疗的反应机制依沙匹隆 在基线时进行安慰剂激发， 在急性和慢性治疗期间进行，使用固定剂量 去甲替林治疗模式设计为产生约等于 反应与无反应患者的大小组，其中 可以测试5-HT 1A受体适应的差异。

This project builds on the investigator's previous work on serotonergic differences between depressed patients who are antidepressant responders vs. those not responding. This study proposes to extend data from the PI's laboratory to date suggesting that chronic, but not acute, 5-HTlA partial agonist administration may have antidepressant effects and desensitize human 5-HT1A receptor-stimulated responses in depressed patients. This proposal seeks to test the hypothesis that standard antidepressant treatment is associated with 5-HT1A receptor-mediated adaptations which will be discriminative of a treatment response to nortriptyline. The project utilizes a standard nortriptyline treatment protocol designed by the investigator to test for biological differences between antidepressant responders vs. antidepressant nonresponders. The nortriptyline treatment design has been used successfully to date to test response groups at different time points during treatment, yielding different response cohorts sufficient to test for biological differences between groups. The present study builds on the investigator's IND# to utilize the 5-HT1A agonist properties of ipsapirone in a challenge paradigm designed to test the ACTH, cortisol, and hypothermic responses of 5-HTlA pre- and postsynaptic receptor subtypes, in a new approach designed to explore the possibility that a 5-HTlA receptor adaptation may underlie a component of the response mechanism to standard antidepressant treatment. lpsapirone and placebo challenges are done at baseline, with repeat challenges performed during acute and chronic treatment, using a fixed dose nortriptyline treatment paradigm designed to yield approximately equal sized groups of responding vs. nonresponding patients in which the differences in 5-HT1A receptor adaptations can be tested.