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

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


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.

Keywords: 5-HTT; Anxiety; Depression; Editing; SSRI; Serotonin(2C); Splicing.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology*
  • Anxiety / drug therapy
  • Anxiety / physiopathology
  • Brain / drug effects
  • Brain / physiopathology
  • Depressive Disorder / drug therapy
  • Depressive Disorder / physiopathology
  • Humans
  • Receptor, Serotonin, 5-HT2C / metabolism*
  • Stress, Psychological / drug therapy
  • Stress, Psychological / physiopathology


  • Antidepressive Agents
  • Receptor, Serotonin, 5-HT2C