Evidence for a complex influence of nicotinic acetylcholine receptors on hippocampal serotonin release

Paul J. Kenny, Sandra E. File, Michael J. Neal

Research output: Contribution to journalArticlepeer-review

90 Scopus citations


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 release. This effect was antagonised by mecamylamine (0.5 μM), indicating an action at nicotinic receptors. Nicotineevoked 5-HT release was not affected by tetrodotoxin (3 μM), cadmium chloride (0.1 mM), or the absence of Ca2+ or Na+ in the superfusion medium. Unexpectedly, higher concentrations 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 μM), 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 explanation is that nicotine stimulates 5-HT release by activating nicotinic heteroreceptors on 5-HT terminals. Mecamylamine (0.5 μM) antagonises this effect, but higher concentrations 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.

Original languageEnglish
Pages (from-to)2409-2414
Number of pages6
JournalJournal of Neurochemistry
Issue number6
StatePublished - 2000
Externally publishedYes


  • 5-Hydroxytryptamine
  • Dorsal hippocampus
  • McN-A-343
  • Mecamylamine
  • Nicotine
  • Paroxetine


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