Presynaptic serotonergic modulation of 5-HT and acetylcholine release in the hippocampus and the cortex of 5-HT1B-receptor knockout mice
| Autor: | Rolf Jackisch, Marie-Christine Buhot, Céline Riegert, Anna Katharina Rothmaier, Susanne Rutz, Jean-Christophe Cassel |
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| Rok vydání: | 2006 |
| Předmět: |
Male
medicine.medical_specialty Serotonin Pyridines Presynaptic Terminals Hippocampus Hippocampal formation Inhibitory postsynaptic potential Serotonergic Tritium Choline Mice Internal medicine medicine Animals Pyrroles 5-HT receptor Cerebral Cortex Mice Knockout Analysis of Variance Dose-Response Relationship Drug Chemistry General Neuroscience Acetylcholine Electric Stimulation Cortex (botany) Serotonin Receptor Agonists Endocrinology Quipazine Receptor Serotonin 5-HT1B Cholinergic Serotonin Antagonists Neuroscience medicine.drug |
| Zdroj: | Brain research bulletin. 70(1) |
| ISSN: | 0361-9230 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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