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Serotonin receptor 1A knockout: an animal model of anxiety-related disorder.

To investigate the contribution of individual serotonin (5-hydroxytryptamine; 5-HT) receptors to mood control, we have used homologous recombination to generate mice lacking specific serotonergic receptor subtypes. In the present report, we demonstrate that mice without 5-HT1A receptors display decreased exploratory activity and increased fear of aversive environments (open or elevated spaces). 5-HT1A knockout mice also exhibited a decreased immobility in the forced swim test, an effect commonly associated with antidepressant treatment. Although 5-HT1A receptors are involved in controlling the activity of serotonergic neurons, 5-HT1A knockout mice had normal levels of 5-HT and 5-hydroxyindoleacetic acid, possibly because of an up-regulation of 5-HT1B autoreceptors. Heterozygote 5-HT1A mutants expressed approximately one-half of wild-type receptor density and displayed intermediate phenotypes in most behavioral tests. These results demonstrate that 5-HT1A receptors are involved in the modulation of exploratory and fear-related behaviors and suggest that reductions in 5-HT1A receptor density due to genetic defects or environmental stressors might result in heightened anxiety.

Pubmed ID: 9826725


  • Ramboz S
  • Oosting R
  • Amara DA
  • Kung HF
  • Blier P
  • Mendelsohn M
  • Mann JJ
  • Brunner D
  • Hen R


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

November 24, 1998

Associated Grants


Mesh Terms

  • Animals
  • Anxiety Disorders
  • Autoradiography
  • Brain
  • Disease Models, Animal
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Mice, Knockout
  • Motor Activity
  • Neurons
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Recombination, Genetic
  • Serotonin
  • Tritium