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Evidence for a Complex Influence of Nicotinic Acetylcholine Receptors on Hippocampal Serotonin Release
Author(s) -
Kenny Paul J.,
File Sandra E.,
Neal Michael J.
Publication year - 2000
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.1471-4159.2000.0752409.x
Subject(s) - mecamylamine , nicotinic agonist , nicotinic antagonist , muscarinic acetylcholine receptor , chemistry , nicotine , acetylcholine , alpha 4 beta 2 nicotinic receptor , endocrinology , ganglion type nicotinic receptor , 5 ht receptor , serotonergic , medicine , inhibitory postsynaptic potential , pharmacology , serotonin , receptor , biology , nicotinic acetylcholine receptor , biochemistry
The effects of nicotine on 5‐hydroxytryptamine (5‐HT)release from serotonergic nerve endings in rat dorsal hippocampal slices werestudied. Nicotine (50‐500 μ M ) caused a concentration‐dependentincrease in 5‐HT release. This effect was antagonised by mecamylamine (0.5μ M ), indicating an action at nicotinic receptors. Nicotine‐evoked5‐HT release was not affected by tetrodotoxin (3 μ M ), cadmiumchloride (0.1 m M ), or the absence of Ca 2+ orNa + in the superfusion medium. Unexpectedly, higher concentrationsof mecamylamine alone (1‐50 μ M ) increased 5‐HT release. Thissuggested the presence of inhibitory input to 5‐HT neurones and that theseinhibitory neurones possess tonically active nicotinic receptors. The effectof mecamylamine (50 μ M ) on 5‐HT release was reduced by themuscarinic M 1 receptor agonist, McN‐A‐343 (100 μ M ), butpirenzepine (0.005‐1 μ M ), which blocks M 1 receptors,alone increased 5‐HT release. Hippocampal serotonergic neurones are known topossess both excitatory nicotinic receptors and inhibitory M 1 receptors. Although there may be several explanations for our results, onepossible explanation is that nicotine stimulates 5‐HT release by activatingnicotinic heteroreceptors on 5‐HT terminals. Mecamylamine (0.5 μ M )antagonises this effect, but higher concentrations increase 5‐HT releaseindirectly by blocking the action of endogenous acetylcholine on nicotinicreceptors situated on cholinergic neurones that provide muscarinic inhibitoryinput to 5‐HT neurones.