Targeted gene deletion of the 5-HT 3A receptor subunit produces an anxiolytic phenotype in mice

Targeted gene deletion of the 5-HT 3A receptor subunit produces an anxiolytic phenotype in mice Anxiety disorders are the most common psychiatric disorders. Typical medications used to treat patients are benzodiazepines or antidepressants that target serotonin (5-HT) activity. The ionotropic 5-HT 3 receptor has emerged as a potential therapeutic target because selective antagonist compounds reduce anxiety in rodents, primates, and humans. 5-HT binds to the extracellular N-terminus of the 5-HT 3A receptor subunit, but receptor activation is also enhanced by distinct allosteric sites. It is not known if specific molecular subunits of the 5-HT 3 receptor modulate anxiety. To address this issue, we characterized anxiety-like behavior of mice with a targeted deletion of the 5-HT 3A receptor subunit gene in the light/dark box, elevated plus maze, and novelty interaction animal models of anxiety. 5-HT 3A null mice exhibited an anxiolytic behavioral phenotype that was highly correlated across behavioral measures. This evidence indicates that the 5-HT 3A molecular subunit influences anxiety-like behavior. Pharmacotherapy that targets specifically the 5-HT 3A receptor subunit may provide a novel treatment for anxiety disorders. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Pharmacology Elsevier

Targeted gene deletion of the 5-HT 3A receptor subunit produces an anxiolytic phenotype in mice

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Publisher
Elsevier
Copyright
Copyright © 2003 Elsevier Science B.V.
ISSN
0014-2999
DOI
10.1016/S0014-2999(02)02960-6
Publisher site
See Article on Publisher Site

Abstract

Anxiety disorders are the most common psychiatric disorders. Typical medications used to treat patients are benzodiazepines or antidepressants that target serotonin (5-HT) activity. The ionotropic 5-HT 3 receptor has emerged as a potential therapeutic target because selective antagonist compounds reduce anxiety in rodents, primates, and humans. 5-HT binds to the extracellular N-terminus of the 5-HT 3A receptor subunit, but receptor activation is also enhanced by distinct allosteric sites. It is not known if specific molecular subunits of the 5-HT 3 receptor modulate anxiety. To address this issue, we characterized anxiety-like behavior of mice with a targeted deletion of the 5-HT 3A receptor subunit gene in the light/dark box, elevated plus maze, and novelty interaction animal models of anxiety. 5-HT 3A null mice exhibited an anxiolytic behavioral phenotype that was highly correlated across behavioral measures. This evidence indicates that the 5-HT 3A molecular subunit influences anxiety-like behavior. Pharmacotherapy that targets specifically the 5-HT 3A receptor subunit may provide a novel treatment for anxiety disorders.

Journal

European Journal of PharmacologyElsevier

Published: Feb 7, 2003

References

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