The Role of Serotonin in Depression
The Role of Serotonin in Depression
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DOI：
10.1016/b978-0-12-374634-4.00030-7
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发表时间：
2010-01-01
期刊：
影响因子：
--
通讯作者：
Lucki, Irwin
中科院分区：
文献类型：
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作者：
Carr, Gregory V.;Lucki, Irwin
关于血清素 (5-HT) 在重度抑郁症 (MDD) 的病因学和治疗中的作用，已经开展了大量研究。本章第一部分总结了 MDD 病因中涉及血清素系统改变的临床证据。普遍的血清素脆弱性已被认为是 MDD 的主要危险因素，由 5-HT 传播不同组成部分的复合危险因素组成。讨论了异常 5-HT 合成、受体功能和遗传多态性的影响。第二部分回顾了一些用于测量抑郁行为和抗抑郁药物（例如选择性血清素再摄取抑制剂（SSRI））疗效的临床前模型和测试。本节重点介绍啮齿动物物种中常用的模型。涵盖了需要急性或长期服用抗抑郁药物才能实现行为改变的模型和测试。第三部分回顾了有关个体 5-HT 受体在抑郁行为的发展和药物治疗中的作用的临床前（啮齿动物）文献。还讨论了 5-HT 消耗和 5-HT 转运蛋白操纵的影响。虽然识别出支持 SSRI 治疗效果的 5-HT 受体可能会导致开发出更有效、副作用更少的抗抑郁药物，但目前尚不清楚 SSRI 的完整抗抑郁作用是否可以通过单一选择性 5-HT 受体激动剂或拮抗剂来重现。
A substantial body of research has developed concerning the role of serotonin (5-HT) in the etiology and treatment of major depressive disorder (MDD). The first section of this chapter summarizes the clinical evidence implicating alterations of the serotonergic system in the etiology of MDD. A general serotonin vulnerability has been proposed as a major risk factor in MDD, consisting of the composite risk factors from different components of 5-HT transmission. The effects of abnormal 5-HT synthesis, receptor function and genetic polymorphisms are discussed. The second section reviews some of the preclinical models and tests that are used to measure depressive behaviors and the efficacy of antidepressant drugs, such as selective serotonin reuptake inhibitors (SSRIs). This section is focused on models that are commonly used in rodent species. Models and tests that require either acute or chronic antidepressant administration to achieve behavioral alterations are covered. The third section reviews the preclinical (rodent) literature concerning the role of individual 5-HT receptors in the development and pharmacological treatment of depressive behaviors. The effects of 5-HT depletion and of manipulation of the 5-HT transporter are also discussed. Although identifying the 5-HT receptors that support the therapeutic effects of SSRIs may lead to the development of more effective antidepressant drugs with fewer side effects, it is unclear whether the complete antidepressant effect of SSRIs can be reproduced by a single selective 5-HT receptor agonist or antagonist.