2. Academic Validation
  3. Ketanserin and tetrabenazine abolish aggression in mice lacking monoamine oxidase A

Ketanserin and tetrabenazine abolish aggression in mice lacking monoamine oxidase A

  • Brain Res. 1999 Jul 24;835(2):104-12. doi: 10.1016/s0006-8993(99)01478-x.
J C Shih 1,  M J Ridd,  K Chen,  W P Meehan,  M P Kung,  I Seif,  E De Maeyer
Affiliations

Affiliation

  • 1 Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, Room 528, 1985 Zonal Avenue, Los Angeles, CA 90033, USA. [email protected]
PMID: 10415365 DOI: 10.1016/s0006-8993(99)01478-x
Abstract

Mice deficient in Monoamine Oxidase A (MAO A) have elevated brain levels of 5-HT and manifest enhanced aggression. We used these mice as a model to study the role of 5-HT in aggression. Our results show that ketanserin and tetrabenazine (TBZ) strikingly abolished the aggressive behavior of MAO A-deficient mice. The anti-aggressive effect of ketanserin may be primarily mediated by 5-HT(2A) receptors. Another specific 5-HT(2A) antagonist, [R-(+)-a-(2, 3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidine-methan ol (MDL 100907), also blocks the aggression of mutant mice but was less dramatic. Ketanserin and TBZ are both antagonists of the vesicular Monoamine Transporter (VMAT2). The anti-aggressive effect of TBZ and part of the effect of ketanserin may be mediated by the VMAT2. Using radioligand binding and autoradiography, we also showed that the numbers of VMAT2, 5-HT(1A), 5-HT(2A) and 5-HT(2C) sites are decreased in brains of mutant mice, which may reflect down-regulation by excess 5-HT. This study suggests that ketanserin and TBZ may be developed as novel anti-aggressive agents.

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