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.
Ramboz
S
S
Center for Neurobiology and Behavior, Columbia University, 722 West 168th Street, New York, NY 10032, USA.
Oosting
R
R
Amara
D A
DA
Kung
H F
HF
Blier
P
P
Mendelsohn
M
M
Mann
J J
JJ
Brunner
D
D
Hen
R
R
D000818:Animals; D001008:Anxiety Disorders / Q000235:genetics* / Q000378:metabolism; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009043:Motor Activity; D009474:Neurons / Q000378:metabolism; D011985:Receptors, Serotonin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D011995:Recombination, Genetic; D012701:Serotonin / Q000378:metabolism; D014316:Tritium
D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D014316:Tritium; D012701:Serotonin