title: Targeted gene deletion of the 5-HT3A receptor subunit produces an anxiolytic phenotype in mice.
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.
authors.affiliation: Ernest Gallo Clinic and Research Center, Department of Neurology, University of California at San Francisco, Emeryville, CA 94608, USA.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Kelley
authors.forename: Alison M
authors.initials: AM
authors.lastname: Bratt
authors.forename: Clyde W
authors.initials: CW
authors.lastname: Hodge
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000523:psychology*; D005106:Exploratory Behavior / Q000502:physiology; D017353:Gene Deletion; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D009043:Motor Activity / Q000235:genetics; D010641:Phenotype; D021122:Protein Subunits; D011985:Receptors, Serotonin / Q000235:genetics*; D044406:Receptors, Serotonin, 5-HT3
chemical_list: D021122:Protein Subunits; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3