Reduction in the density and expression, but not G-protein coupling, of serotonin receptors (5-HT(1A)) in 5-HT transporter knock-out mice: Gender and brain region differences

Q. Li, C. Wichems, A. Heils, K. P. Lesch, D. L. Murphy

Research output: Contribution to journalArticlepeer-review

Abstract

The aim of the present study was to investigate the mechanisms underlying the desensitization of 5-HT(1A) receptors in the dorsal raphe and hypothalamus of serotonin (5-HT) transporter knock-out mice (5-HTT -/-). The density of 5-HT(1A) 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-HT(1A) receptors also was decreased significantly in several nuclei of the hypothalamus, amygdala, and septum of female 5-HTT -/- mice. 5-HT(1A) 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-HT(1A) receptors and G-protein levels in most brain regions were not reduced significantly, except that G(o) and G(i1) proteins were reduced modestly in the midbrain of 5-HTT -/- mice. These data suggest that the desensitization of 5-HT(1A) receptors in 5-HTT -/- mice may be attributable to a reduction in the density of 5-HT(1A) receptors. This reduction is brain region-specific and more extensive in the female mice. The reduction in the density of 5-HT(1A) receptors may be mediated partly by reduction in the gene expression of 5-HT(1A) 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-HT(1A) receptors are unlikely to be involved in the desensitization of 5-HT(1A) receptors in 5-HTT -/- mice.

Original languageEnglish (US)
Pages (from-to)7888-7895
Number of pages8
JournalJournal of Neuroscience
Volume20
Issue number21
DOIs
StatePublished - Nov 1 2000

Keywords

  • 5-HT transporter knock-out mice
  • 5-HT(1A) mRNA
  • 5-HT(1A) receptors
  • Autoradiography
  • Competitive RT-PCR
  • G-protein coupling
  • Gender difference
  • Hypothermia
  • In situ hybridization

ASJC Scopus subject areas

  • Neuroscience(all)

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