5-羟色胺（2C）受体在抗抑郁药物作用机制中的作用争议。

Controversies on the role of 5-HT(2C) receptors in the mechanisms of action of antidepressant drugs.

作者信息

Martin Cedric B P, Hamon Michel, Lanfumey Laurence, Mongeau Raymond

机构信息

INSERM UMR S894, Centre de Psychiatrie et Neurosciences, Paris, France; UPMC, Univ Paris 06, Paris, France; Paris Descartes, Univ Paris 05, Paris, France.

INSERM UMR S894, Centre de Psychiatrie et Neurosciences, Paris, France; Paris Descartes, Univ Paris 05, Paris, France; EA4475 - Pharmacologie de la circulation cérébrale, Paris, France.

出版信息

Neurosci Biobehav Rev. 2014 May;42:208-23. doi: 10.1016/j.neubiorev.2014.03.001. Epub 2014 Mar 11.

DOI:10.1016/j.neubiorev.2014.03.001

PMID:24631644

Abstract

Evidence from the various sources indicates alterations in 5-HT2C receptor functions in anxiety, depression and suicide, and other stress-related disorders treated with antidepressant drugs. Although the notion of a 5-HT2C receptor desensitization following antidepressant treatments is rather well anchored in the literature, this concept is mainly based on in vitro assays and/or behavioral assays (hypolocomotion, hyperthermia) that have poor relevance to anxio-depressive disorders. Our objective herein is to provide a comprehensive overview of the studies that have assessed the effects of antidepressant drugs on 5-HT2C receptors. Relevant molecular (second messengers, editing), neurochemical (receptor binding and mRNA levels), physiological (5-HT2C receptor-induced hyperthermia and hormone release), behavioral (5-HT2C receptor-induced changes in feeding, anxiety, defense and motor activity) data are summarized and discussed. Setting the record straight about drug-induced changes in 5-HT2C receptor function in specific brain regions should help to determine which pharmacotherapeutic strategy is best for affective and anxiety disorders.

摘要

来自各种来源的证据表明，5-羟色胺2C受体功能在焦虑症、抑郁症和自杀以及其他用抗抑郁药物治疗的应激相关障碍中发生了改变。尽管抗抑郁治疗后5-羟色胺2C受体脱敏的概念在文献中有相当充分的依据，但这一概念主要基于体外试验和/或行为试验（运动减少、体温过高），而这些试验与焦虑抑郁障碍的相关性较差。我们在此的目的是全面概述评估抗抑郁药物对5-羟色胺2C受体影响的研究。总结并讨论了相关的分子（第二信使、编辑）、神经化学（受体结合和mRNA水平）、生理学（5-羟色胺2C受体诱导的体温过高和激素释放）、行为学（5-羟色胺2C受体诱导的进食、焦虑、防御和运动活动变化）数据。澄清药物在特定脑区引起的5-羟色胺2C受体功能变化，有助于确定哪种药物治疗策略对情感障碍和焦虑症最为有效。