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| Research article summary (published May 2006): |
Presynaptic serotonergic modulation of 5-HT and acetylcholine release in the hippocampus and the cortex of 5-HT1B-receptor knockout mice.
Full Abstract
Lesioning of serotonergic afferents increases hippocampal ACh release and attenuates memory deficits produced by cholinergic lesions. Improved memory performance described in 5-HT1B-knockout (KO) mice might thus be due to a weaker 5-HT1B-mediated inhibitory influence of 5-HT on hippocampal ACh release. The selective delay-dependent impairment of working memory observed in these KO mice suggests, however, that cortical regions also participate in task performance, possibly via indirect influences of 5-HT on ACh release. To provide neuropharmacological support for these hypotheses we measured evoked ACh and 5-HT release in hippocampal and cortical slices of wild-type (WT) and 5-HT1B KO mice. Superfused slices (preincubated with [3H]choline or [3H]5-HT) were electrically stimulated in the absence or presence of 5-HT1B receptor ligands. In hippocampus and cortex, 5-HT1B agonists decreased and antagonists increased 5-HT release in WT, but not in 5-HT1B KO mice. In 5-HT1B KO mice, 5-HT release was enhanced in both structures, while ACh release (in nCi) was reduced. ACh release was inhibited by 5-HT1B agonists in hippocampal (not cortical) slices of WT but not of 5-HT1B KO mice. Our data (i) confirm the absence of autoinhibition of 5-HT release in 5-HT1B-KO mice, (ii) demonstrate a reduced release of ACh, and the absence of 5-HT1B-receptor-mediated inhibition of ACh release, in the hippocampus and cortex of 5-HT1B-KO mice, and (iii) are compatible with an indirect role of cortical ACh in the working memory impairment observed in these KO mice.
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Author information
Author/s: Rutz, Susanne (S); Riegert, Céline (C); Rothmaier, Anna Katharina (AK); Buhot, Marie-Christine (MC); Cassel, Jean-Christophe (JC); Jackisch, Rolf (R);
Affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, Laboratory of Neuropharmacology, University of Freiburg, Hansastrasse 9A, D-79104 Freiburg, Germany.
Journal and publication information
Publication Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
Journal: Brain research bulletin (Brain Res Bull), published in United States. (Language: eng)
Reference: 2006-Jun; vol 70 (issue 1) : pp 81-93
Dates: Created 2006/06/05; Completed 2006/09/05; Revised 2006/11/15;
PMID: 16750486, status: MEDLINE (last retrieval date: 12/26/2008)
Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.
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