Serotonin1A receptor acts during development to establish normal anxiety-like behaviour in the adult

Nature. 2002 Mar 28;416(6879):396-400. doi: 10.1038/416396a.


Serotonin is implicated in mood regulation, and drugs acting via the serotonergic system are effective in treating anxiety and depression. Specifically, agonists of the serotonin1A receptor have anxiolytic properties, and knockout mice lacking this receptor show increased anxiety-like behaviour. Here we use a tissue-specific, conditional rescue strategy to show that expression of the serotonin1A receptor primarily in the hippocampus and cortex, but not in the raphe nuclei, is sufficient to rescue the behavioural phenotype of the knockout mice. Furthermore, using the conditional nature of these transgenic mice, we suggest that receptor expression during the early postnatal period, but not in the adult, is necessary for this behavioural rescue. These findings show that postnatal developmental processes help to establish adult anxiety-like behaviour. In addition, the normal role of the serotonin1A receptor during development may be different from its function when this receptor is activated by therapeutic intervention in adulthood.

Publication types

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

MeSH terms

  • Aging / physiology
  • Animals
  • Anxiety* / metabolism
  • Brain / metabolism
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Knockout
  • Phenotype
  • Prosencephalon / metabolism
  • Prosencephalon / physiology
  • Receptors, Serotonin / genetics
  • Receptors, Serotonin / physiology*
  • Receptors, Serotonin, 5-HT1
  • Serotonin Receptor Agonists / pharmacology


  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Serotonin Receptor Agonists