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Serotonergic Facilitation of Acetylcholine Release In Vivo from Rat Dorsal Hippocampus via Serotonin 5‐HT 3 Receptors
Author(s) -
Console Silvana,
Bertorelli Rosalia,
Russi Giovanni,
Zambelli Matilde,
Ladinsky Herbert
Publication year - 1994
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1994.62062254.x
Subject(s) - ritanserin , chemistry , pharmacology , 5 ht receptor , serotonin , acetylcholine , microdialysis , metergoline , 5 ht3 receptor , agonist , serotonergic , receptor antagonist , neurotransmitter , endocrinology , medicine , receptor , antagonist , biology , extracellular , biochemistry
The serotonin (5‐HT) releaser d ‐fenfluramine and its active metabolite d ‐norfenfluramine, or the 5‐HT‐uptake inhibitor citalopram, by increasing synaptic 5‐HT availability, facilitated in vivo release of acetylcholine (ACh) from dorsal hippocampi of freely moving rats as determined by the microdialysis technique. The effects of d ‐norfenfluramine (7.5 mg/kg i.p.) and citalopram (10 μ M , applied by reverse dialysis) were prevented by a 14‐day chemical lesion of the raphe nuclei, suggesting mediation by the 5‐HT system in the cholinergic action of the drugs. The increase in extracellular ACh content induced by d ‐norfenfluramine (5 mg/kg i.p.) was antagonized by the 5‐HT 3 receptor antagonists tropisetron (0.5 mg/kg i.p.) and DAU 6215 (60 μg/kg i.p.), but not by the mixed 5‐HT 1 and 5‐HT 2 receptor antagonist metergoline (2 mg/kg s.c.). In accordance with an involvement of the 5‐HT 3 receptor in the ACh facilitation induced by d‐norfenfluramine is the finding that the selective 5‐HT 3 receptor agonist 2‐methyl‐serotonin (250 μg i.c.v., or 10 μ M applied by reverse dialysis) raised ACh release. The effect of the intracerebroventricular drug was prevented by the 5‐HT 3 antagonists DAU 6215 (60 μg/kg i.p.) and ondansetron (60 μg/kg s.c.). These antagonists by themselves did not modify the basal ACh release, indicating that 5‐HT does not tonically activate the 5‐HT 3 receptors involved. In conclusion, the overall regulatory control exerted by 5‐HT in vivo is to facilitate hippocampal ACh release. This is mediated by 5‐HT 3 receptors probably located in the dorsal hippocampi.