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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2006-8-25
pubmed:abstractText
Decreased serotonin (5-HT) transmission is thought to underlie several mental diseases, including depression and feeding disorders. However, whether deficits in genes encoding G protein-coupled receptors may down-regulate the activity of 5-HT neurons is unknown currently. Based on recent evidence that stress-induced anorexia may involve 5-HT(4)receptors (5-HT(4)R), we measured various aspects of 5-HT function in 5-HT(4)R knock-out (KO) mice. When compared to dorsal raphe nucleus (DRN) 5-HT neurons from wild-type mice, those from 5-HT(4)R KO mice exhibited reduced spontaneous electrical activity. This reduced activity was associated with diminished tissue levels of 5-HT and its main metabolite, 5-hydroxyindole acetic acid (5-HIAA). Cumulative, systemic doses of the 5-HT uptake blocker citalopram, that reduced 5-HT cell firing by 30% in wild-type animals, completely inhibited 5-HT neuron firing in the KO mice. This effect was reversed by administration of the 5-HT(1A) receptor (5-HT(1A)R) antagonist, WAY100635, in mice of both genotypes. Other changes in DRN of the KO mice included increases in the levels of 5-HT plasma membrane transporter sites and mRNA, as well as a decrease in the density of 5-HT(1A)R sites without any change in 5-HT(1A) mRNA content. With the exception of increased 5-HT turnover index in the hypothalamus and nucleus accumbens and a decreased density of 5-HT(1A)R sites in the dorsal hippocampus (CA1) and septum, no major changes were detected in 5-HT territories of projection, suggesting region-specific adaptive changes. The mechanisms whereby 5-HT(4)R mediate a tonic positive influence on the firing activity of DRN 5-HT neurons and 5-HT content remain to be determined.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0953-816X
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1053-62
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Adaptive changes in serotonin neurons of the raphe nuclei in 5-HT(4) receptor knock-out mouse.
pubmed:affiliation
Unité mixte de Recherche Centre National de la Recherche Scientifique 5203, INSERM, U661, University Montpellier I, University Montpellier II, Institut de Génomique Fonctionnelle, Département de Neurobiologie, Montpellier, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't