Regulation of Serotonin Release in the Frontal Cortex and Ventral Hippocampus of Homozygous Mice Lacking 5-HT1B Receptors: In Vivo Microdialysis Studies |
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Authors: | A-C Trillat I Malagié K Scearce D Pons M-C Anmella C Jacquot R Hen A M Gardier |
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Institution: | Laboratoire de Neuropharmacologie, JE MESR 92-372, Facultéde Pharmacie, Universitéde Paris-Sud, Châtenay-Malabry, France;and; Center for Neurobiology and Behavior, Columbia University, New York, New York, U.S.A. |
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Abstract: | Abstract: To assess the involvement of the serotonin receptor subtype 5-HT1B as terminal autoreceptor regulating 5-HT release in mice, we compared basal values and potassium-evoked changes of extracellular 5-HT levels obtained by in vivo microdialysis in two serotoninergic terminal projection areas of conscious wild-type mice with those measured in homozygous mutant mice lacking the gene encoding the 5-HT1B receptor. In the frontal cortex and ventral hippocampus, basal and K+-evoked 5-HT release did not differ between the two strains of mice studied. The infusion via reverse microdialysis of the selective 5-HT1B receptor agonist CP-93,129 (500 n M ) decreased significantly K+-evoked 5-HT release in the frontal cortex (by ?44%) and ventral hippocampus (by ?32%) of wild-type mice but had no effect in mutants. In a similar manner, the mixed 5-HT1B-5-HT1D receptor agonist sumatriptan (800 n M ) decreased significantly K+-evoked 5-HT release in the frontal cortex (by ?46%) of wild-type mice but had no effect in mutants. These results demonstrated that 5-HT1B knockout mice are not as sensitive to full (CP-93,129) and mixed (sumatriptan) 5-HT1B receptor agonists as are wild-type mice. These data provide in vivo evidence that, in mice, 5-HT1B, but not 5-HT1D, autoreceptors inhibit 5-HT release at nerve terminals located in the frontal cortex and ventral hippocampus. |
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Keywords: | 5-Hydroxytryptamine 5-Hydroxytryptamine1B receptor Knockout mice Intracerebral microdialysis Serotonin release |
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