Ketanserin and tetrabenazine abolish aggression in mice lacking monoamine oxidase A
| Autor: | Jean C. Shih, Michael James Ridd, Woerner P. Meehan, Kevin Chen, Isabelle Seif, Edward De Maeyer, Mei-Ping Kung |
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| Rok vydání: | 1999 |
| Předmět: |
Male
medicine.medical_specialty Ketanserin Monoamine oxidase Tetrabenazine Drug Evaluation Preclinical Pharmacology Mice Radioligand Assay Piperidines Internal medicine medicine Animals Monoamine Oxidase Molecular Biology 5-HT receptor Mice Knockout Neurotransmitter Agents Adrenergic Uptake Inhibitors biology Chemistry General Neuroscience Antagonist Brain Corpus Striatum Frontal Lobe Aggression Fluorobenzenes Vesicular monoamine transporter Endocrinology biology.protein Serotonin Antagonists Neurology (clinical) Serotonin Monoamine oxidase A Developmental Biology medicine.drug |
| Zdroj: | Brain Research. 835:104-112 |
| ISSN: | 0006-8993 |
| DOI: | 10.1016/s0006-8993(99)01478-x |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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