Targeted gene deletion of the 5-HT3A receptor subunit produces an anxiolytic phenotype in mice

Eur J Pharmacol. 2003 Feb 7;461(1):19-25. doi: 10.1016/s0014-2999(02)02960-6.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / genetics
  • Anxiety / psychology*
  • Exploratory Behavior / physiology
  • Gene Deletion
  • Male
  • Maze Learning / physiology
  • Mice
  • Mice, Mutant Strains
  • Motor Activity / genetics
  • Phenotype
  • Protein Subunits
  • Receptors, Serotonin / genetics*
  • Receptors, Serotonin, 5-HT3


  • Protein Subunits
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT3