5-HT1A RECEPTOR ADAPTATIONS IN ANTIDEPRESSANT RESPONSE

这个项目建立在研究人员之前关于5-羟色胺能的工作基础上 抑郁症患者作为抗抑郁药物应答者的差异 对那些没有反应的人。这项研究建议将数据从 Pi的实验室到目前为止表明5-HTlA是慢性的，但不是急性的 部分服用激动剂可能有抗抑郁作用和 抑郁症患者脱敏5-HT1a受体刺激的反应 病人。这一提议试图检验这样一种假设，即标准 抗抑郁治疗与5-HT1a受体介导相关 对治疗反应具有歧视性的适应 去甲替林。 该项目使用设计的标准去甲替林治疗方案 由调查人员来测试生物差异 抗抑郁剂应答者与抗抑郁剂无应答者。这个 去甲替林治疗设计到目前为止已成功用于试验 在治疗过程中的不同时间点的反应组，产生 足以测试生物差异的不同反应队列 在小组之间。 本研究以研究人员的IND#为基础，利用5-HT1a 伊帕沙必龙在挑战范式中的激动剂特性 5-HTlA受体拮抗剂ACTH、皮质醇和低温反应的研究 突触后受体亚型，用一种新的方法来探索 5-HTlA受体适应的可能性可能是 对标准抗抑郁药物治疗的反应机制。伊普沙普龙 而安慰剂挑战是在基线上进行的，重复挑战 在急性和慢性治疗期间，使用固定剂量 去甲替林治疗方案设计为产生大致相同的疗效 有反应的和无反应的患者的大小分组 5-HT1a受体适应性的差异是可以测试的。

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.