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The Journal of Neuroscience, November 1, 2000, 20(21):7888-7895
Reduction in the Density and Expression, But Not G-Protein
Coupling, of Serotonin Receptors (5-HT1A) in 5-HT
Transporter Knock-Out Mice: Gender and Brain Region Differences
Qian
Li1,
Christine
Wichems1,
Armin
Heils1,
Klaus-Peter
Lesch2, and
Dennis L.
Murphy1
1 Laboratory of Clinical Science, National Institute of
Mental Health, National Institutes of Health Clinical Center, Bethesda,
Maryland 20892-1264, and 2 Department of Psychiatry,
University of Würzburg, 97080 Würzburg, Germany
The aim of the present study was to investigate the mechanisms
underlying the desensitization of 5-HT1A receptors in the
dorsal raphe and hypothalamus of serotonin (5-HT) transporter knock-out mice (5-HTT  /). The density of 5-HT1A receptors in the
dorsal raphe was reduced in both male and female 5-HTT / mice. This reduction was more extensive in female than in male 5-HTT / mice.
8-OH-DPAT-induced hypothermia was absent in female 5-HTT / and
markedly attenuated in 5-HTT +/ mice. The density of 5-HT1A receptors also was decreased significantly in
several nuclei of the hypothalamus, amygdala, and septum of female
5-HTT / mice. 5-HT1A receptor mRNA was reduced
significantly in the dorsal raphe region, but not in the
hypothalamus or hippocampus, of female 5-HTT +/ and 5-HTT
/ mice. G-protein coupling to 5-HT1A receptors and G-protein levels in most brain regions were not reduced
significantly, except that Go and Gi1 proteins
were reduced modestly in the midbrain of 5-HTT / mice. These data
suggest that the desensitization of 5-HT1A receptors in
5-HTT / mice may be attributable to a reduction in the density of
5-HT1A receptors. This reduction is brain region-specific
and more extensive in the female mice. The reduction in the density of
5-HT1A receptors may be mediated partly by reduction in the
gene expression of 5-HT1A receptors in the dorsal raphe,
but also by other mechanisms in the hypothalamus of 5-HTT / female
mice. Finally, alterations in G-protein coupling to 5-HT1A
receptors are unlikely to be involved in the desensitization of
5-HT1A receptors in 5-HTT / mice.
Key words:
5-HT1A receptors; 5-HT1A mRNA; 5-HT transporter knock-out mice; G-protein coupling; hypothermia; gender difference; autoradiography; competitive RT-PCR; in situ
hybridization
Copyright © 2000 Society for Neuroscience 0270-6474/00/20217888-08$05.00/0
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