Elevated anxiety and antidepressant-like responses in serotonin 5-HT1A receptor mutant mice.
The brain serotonin (5-hydroxytryptamine; 5-HT) system is a powerful modulator of emotional processes and a target of medications used in the treatment of psychiatric disorders. To evaluate the contribution of serotonin 5-HT1A receptors to the regulation of these processes, we have used gene-targeting technology to generate 5-HT1A receptor-mutant mice. These animals lack functional 5-HT1A receptors as indicated by receptor autoradiography and by resistance to the hypothermic effects of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Homozygous mutants display a consistent pattern of responses indicative of elevated anxiety levels in open-field, elevated-zero maze, and novel-object assays. Moreover, they exhibit antidepressant-like responses in a tail-suspension assay. These results indicate that the targeted disruption of the 5-HT1A receptor gene leads to heritable perturbations in the serotonergic regulation of emotional state. 5-HT1A receptor-null mutant mice have potential as a model for investigating mechanisms through which serotonergic systems modulate affective state and mediate the actions of psychiatric drugs.
Heisler
L K
LK
Department of Psychiatry and Center for Neurobiology and Psychiatry, University of California, San Francisco, 401 Parnassus Avenue, San Francisco, CA 94143-0984, USA.
Chu
H M
HM
Brennan
T J
TJ
Danao
J A
JA
Bajwa
P
P
Parsons
L H
LH
Tecott
L H
LH
D000818:Animals; D001007:Anxiety / Q000235:genetics*; D001921:Brain / Q000502:physiology*; D003863:Depression / Q000235:genetics*; D018390:Gene Targeting; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D011985:Receptors, Serotonin / Q000235:genetics*
D011985:Receptors, Serotonin