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PMID: 11050108 Published · ppublish English Journal Article

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.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 20 ·No. 21 ·2000-11-01 ·Pages 7888-95

Li Q, Wichems C, Heils A, Lesch KP, Murphy DL

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.

MeSH Terms
Amygdala/cytology,metabolism Animals Autoradiography Binding, Competitive/drug effects Carrier Proteins/genetics,metabolism Female GTP-Binding Proteins/metabolism Guanosine 5'-O-(3-Thiotriphosphate)/pharmacokinetics Heterozygote Hippocampus/cytology,metabolism Homozygote Hypothalamus/cytology,metabolism Immunoblotting Male Membrane Glycoproteins/deficiency,genetics,metabolism Membrane Transport Proteins Mice Mice, Knockout Nerve Tissue Proteins Organ Specificity RNA, Messenger/metabolism Raphe Nuclei/cytology,metabolism Receptors, Serotonin/genetics,metabolism Receptors, Serotonin, 5-HT1 Reverse Transcriptase Polymerase Chain Reaction Septum of Brain/cytology,metabolism Serotonin Antagonists/pharmacokinetics Serotonin Plasma Membrane Transport Proteins Serotonin Receptor Agonists/pharmacology Sex Factors
Chemicals
Carrier Proteins Membrane Glycoproteins Membrane Transport Proteins Nerve Tissue Proteins RNA, Messenger Receptors, Serotonin Receptors, Serotonin, 5-HT1 Serotonin Antagonists Serotonin Plasma Membrane Transport Proteins Serotonin Receptor Agonists Slc6a4 protein, mouse Guanosine 5'-O-(3-Thiotriphosphate) GTP-Binding Proteins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Li Q
Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health Clinical Center, Bethesda, Maryland 20892-1264, USA. qianli@codon.nih.gov
Wichems C
Heils A
Lesch K P
Murphy D L
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Email
qianli@codon.nih.gov
Published
2000-11-01
Pages
7888-95
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6772750
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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