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Elevated anxiety and antidepressant-like responses in serotonin 5-HT1A receptor mutant mice.

The brain serotonin (5-hydroxytryptamine; 5-HT) system is a powerful modulator of emotional processes and a target of medications used in the treatment of psychiatric disorders. To evaluate the contribution of serotonin 5-HT1A receptors to the regulation of these processes, we have used gene-targeting technology to generate 5-HT1A receptor-mutant mice. These animals lack functional 5-HT1A receptors as indicated by receptor autoradiography and by resistance to the hypothermic effects of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Homozygous mutants display a consistent pattern of responses indicative of elevated anxiety levels in open-field, elevated-zero maze, and novel-object assays. Moreover, they exhibit antidepressant-like responses in a tail-suspension assay. These results indicate that the targeted disruption of the 5-HT1A receptor gene leads to heritable perturbations in the serotonergic regulation of emotional state. 5-HT1A receptor-null mutant mice have potential as a model for investigating mechanisms through which serotonergic systems modulate affective state and mediate the actions of psychiatric drugs.

Pubmed ID: 9844013

Authors

  • Heisler LK
  • Chu HM
  • Brennan TJ
  • Danao JA
  • Bajwa P
  • Parsons LH
  • Tecott LH

Journal

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

Publication Data

December 8, 1998

Associated Grants

None

Mesh Terms

  • Animals
  • Anxiety
  • Brain
  • Depression
  • Gene Targeting
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mutation
  • Receptors, Serotonin