title: Presynaptic serotonergic modulation of 5-HT and acetylcholine release in the hippocampus and the cortex of 5-HT1B-receptor knockout mice.
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.
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, Laboratory of Neuropharmacology, University of Freiburg, Hansastrasse 9A, D-79104 Freiburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Rutz
authors.forename: Céline
authors.initials: C
authors.lastname: Riegert
authors.forename: Anna Katharina
authors.initials: AK
authors.lastname: Rothmaier
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Buhot
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Cassel
authors.forename: Rolf
authors.initials: R
authors.lastname: Jackisch
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects / Q000528:radiation effects; D002794:Choline / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D011814:Quipazine / Q000031:analogs & derivatives / Q000494:pharmacology; D044302:Receptor, Serotonin, 5-HT1B / Q000172:deficiency*; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014316:Tritium / Q000378:metabolism
chemical_list: D011725:Pyridines; D011758:Pyrroles; D044302:Receptor, Serotonin, 5-HT1B; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014316:Tritium; C065046:3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo(3,2-b)pyrid-5-one; D012701:Serotonin; D011814:Quipazine; C031227:6-nitroquipazine; D002794:Choline; D000109:Acetylcholine