Serotonin receptor 1A knockout: an animal model of anxiety-related disorder.
To investigate the contribution of individual serotonin (5-hydroxytryptamine; 5-HT) receptors to mood control, we have used homologous recombination to generate mice lacking specific serotonergic receptor subtypes. In the present report, we demonstrate that mice without 5-HT1A receptors display decreased exploratory activity and increased fear of aversive environments (open or elevated spaces). 5-HT1A knockout mice also exhibited a decreased immobility in the forced swim test, an effect commonly associated with antidepressant treatment. Although 5-HT1A receptors are involved in controlling the activity of serotonergic neurons, 5-HT1A knockout mice had normal levels of 5-HT and 5-hydroxyindoleacetic acid, possibly because of an up-regulation of 5-HT1B autoreceptors. Heterozygote 5-HT1A mutants expressed approximately one-half of wild-type receptor density and displayed intermediate phenotypes in most behavioral tests. These results demonstrate that 5-HT1A receptors are involved in the modulation of exploratory and fear-related behaviors and suggest that reductions in 5-HT1A receptor density due to genetic defects or environmental stressors might result in heightened anxiety.
Pubmed ID: 9826725 RIS Download
Animals | Anxiety Disorders | Autoradiography | Brain | Disease Models, Animal | Female | Humans | Male | Mice | Mice, Inbred C57BL | Mice, Inbred Strains | Mice, Knockout | Motor Activity | Neurons | Receptors, Serotonin | Receptors, Serotonin, 5-HT1 | Recombination, Genetic | Serotonin | Tritium