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.
European Journal of Pharmacology – Elsevier
Published: Feb 7, 2003
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