5-HT(1A) [corrected] receptors in mood and anxiety: recent insights into autoreceptor versus heteroreceptor function

Psychopharmacology (Berl). 2014 Feb;231(4):623-36. doi: 10.1007/s00213-013-3389-x. Epub 2013 Dec 12.


Rationale: Serotonin (5-HT) neurotransmission is intimately linked to anxiety and depression and a diverse body of evidence supports the involvement of the main inhibitory serotonergic receptor, the serotonin-1A (5-HT(1A)) subtype, in both disorders.

Objectives: In this review, we examine the function of 5-HT(1A) receptor subpopulations and re-interpret our understanding of their role in mental illness in light of new data, separating both spatial (autoreceptor versus heteroreceptor) and the temporal (developmental versus adult) roles of the endogenous 5-HT(1A) receptors, emphasizing their distinct actions in mediating anxiety and depression-like behaviors.

Results: It is difficult to unambiguously distinguish the effects of different populations of the 5-HT(1A) receptors with traditional genetic animal models and pharmacological approaches. However, with the advent of novel genetic systems and subpopulation-selective pharmacological agents, direct evidence for the distinct roles of these populations in governing emotion-related behavior is emerging.

Conclusions: There is strong and growing evidence for a functional dissociation between auto- and heteroreceptor populations in mediating anxiety and depressive-like behaviors, respectively. Furthermore, while it is well established that 5-HT(1A) receptors act developmentally to establish normal anxiety-like behaviors, the developmental role of 5-HT(1A) heteroreceptors is less clear, and the specific mechanisms underlying the developmental role of each subpopulation are likely to be key elements determining mood control in adult subjects.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anxiety / drug therapy
  • Anxiety / genetics
  • Anxiety / physiopathology*
  • Autoreceptors / genetics
  • Autoreceptors / metabolism
  • Depressive Disorder / drug therapy
  • Depressive Disorder / genetics
  • Depressive Disorder / physiopathology
  • Humans
  • Mood Disorders / drug therapy
  • Mood Disorders / genetics
  • Mood Disorders / physiopathology*
  • Polymorphism, Genetic
  • Receptor, Serotonin, 5-HT1A / genetics
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Serotonin Agents / pharmacology
  • Serotonin Agents / therapeutic use


  • Autoreceptors
  • Serotonin Agents
  • Receptor, Serotonin, 5-HT1A