The serotonergic system and anxiety

Neuromolecular Med. 2004;5(1):27-40. doi: 10.1385/NMM:5:1:027.


The wide use of serotonin reuptake inhibitors and serotonin receptor agonists in anxiety disorders has suggested a key role for the modulatory neurotransmitter in anxiety. However, serotonin's specific role is still uncertain. This article reviews the literature concerning how and where serotonergic agents modulate anxiety. Varying and sometimes conflicting data from human and animal studies argue for both anxiolytic and anxiogenic roles for serotonin, depending on the specific disorder, structure, or behavioral task studied. However, recent data from molecular genetic studies in the mouse point toward two important roles for the serotonin 1A receptor. In development, serotonin acts through this receptor to promote development of the circuitry necessary for normal anxiety-like behaviors. In adulthood, serotonin reuptake inhibitors act through the same receptor to stimulate neurogenesis and reduce anxiety-like behaviors. These studies highlight that the complex serotonin system likely plays various roles in the regulation of anxiety both during development and in adulthood.

Publication types

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

MeSH terms

  • Animals
  • Anxiety Disorders / drug therapy
  • Anxiety Disorders / metabolism
  • Anxiety Disorders / physiopathology*
  • Brain / drug effects
  • Brain / metabolism
  • Brain / physiopathology*
  • Brain Chemistry / drug effects
  • Brain Chemistry / physiology*
  • Disease Models, Animal
  • Humans
  • Receptor, Serotonin, 5-HT1A / metabolism
  • Serotonin / metabolism*
  • Serotonin 5-HT1 Receptor Agonists
  • Serotonin Receptor Agonists / pharmacology
  • Serotonin Uptake Inhibitors / pharmacology


  • Serotonin 5-HT1 Receptor Agonists
  • Serotonin Receptor Agonists
  • Serotonin Uptake Inhibitors
  • Receptor, Serotonin, 5-HT1A
  • Serotonin