title: Acetylcholine mediates the effects of fenfluramine on dentate granule cell excitability in the rat.
abstract: Reactivity of the hippocampal system to stimulation of its main afferent, the perforant path, was studied in the intact, anesthetized rat. Parentral administration of fenfluramine caused a marked elevation of population spike response to perforant path stimulation. An injection of atropine before, but not after fenfluramine, blocked the potentiating effect of fenfluramine. The atropine blockade was dose-dependent and not mimicked by the peripheral muscarinic receptor antagonist methyl atropine. This effect of fenfluramine was also prevented by an injection of the 5-HT receptor antagonist spiperone. The effect of fenfluramine was mimicked by the anticholinesterase physostigmine, which was not affected by spiperone pretreatment. It is proposed that release of 5-HT (5-hydroxytryptamine) by fenfluramine potentiates reactivity to afferent stimulation by interacting with cholinergic terminals in the hippocampus.
authors.affiliation: Department of Neurobiology, Weizmann Institute, Rehovot, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Levkovitz
authors.forename: M
authors.initials: M
authors.lastname: Segal
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001286:Atropine Derivatives / Q000494:pharmacology; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005071:Evoked Potentials / Q000187:drug effects; D005277:Fenfluramine / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D008297:Male; D010276:Parasympatholytics / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D013134:Spiperone / Q000494:pharmacology
chemical_list: D001286:Atropine Derivatives; D010276:Parasympatholytics; D005277:Fenfluramine; D012701:Serotonin; D013134:Spiperone; D001285:Atropine; C006649:methylatropine; D010830:Physostigmine; D000109:Acetylcholine