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- Title
Evidence for a Complex Influence of Nicotinic Acetylcholine Receptors on Hippocampal Serotonin Release.
- Authors
Kenny, Paul J.; File, Sandra E.; Neal, Michael J.
- Abstract
Abstract: The effects of nicotine on 5-hydroxytryptamine (5-HT) release from serotonergic nerve endings in rat dorsal hippocampal slices were studied. Nicotine (50-500 µM) caused a concentration-dependent increase in 5-HT re-lease. This effect was antagonised by mecamylamine (0.5 µM), indicating an action at nicotinic receptors. Nicotine-evoked 5-HT release was not affected by tetrodotoxin (3 µM), cadmium chloride (0.1 mM), or the absence of Ca 21 or Na 1 in the superfusion medium. Unexpectedly, higher con-centrations of mecamylamine alone (1-50 µM) increased 5-HT release. This suggested the presence of inhibitory input to 5-HT neurones and that these inhibitory neurones possess tonically active nicotinic receptors. The effect of mecamylamine (50 µM) on 5-HT release was reduced by the muscarinic M1 receptor agonist, McN-A-343 (100 mM), but pirenzepine (0.005-1 µM), which blocks M1 receptors, alone increased 5-HT release. Hippocampal serotonergic neurones are known to possess both excitatory nicotinic receptors and inhibitory M1 receptors. Although there may be several explanations for our results, one possible expla-nation is that nicotine stimulates 5-HT release by activating nicotinic heteroreceptors on 5-HT terminals. Mecamyl-amine (0.5 mM) antagonises this effect, but higher concen-trations increase 5-HT release indirectly by blocking the action of endogenous acetylcholine on nicotinic receptors situated on cholinergic neurones that provide muscarinic inhibitory input to 5-HT neurones. Key Words: Nico-tine--Mecamylamine--McN-A-343--Paroxetine--5-Hy-droxytryptamine--Dorsal hippocampus.
- Subjects
NICOTINIC receptors; SEROTONIN; MECAMYLAMINE; MUSCARINIC receptors
- Publication
Journal of Neurochemistry, 2000, Vol 75, Issue 6, p2409
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1046/j.1471-4159.2000.0752409.x