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

Academic Article
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Overview

authors

  • Kenny, Paul
  • File, S. E.
  • Neal, M. J.

publication date

  • 2000

journal

  • Journal of Neurochemistry  Journal

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 microM:) caused a concentration-dependent increase in 5-HT release. This effect was antagonised by mecamylamine (0.5 microM:), indicating an action at nicotinic receptors. Nicotine-evoked 5-HT release was not affected by tetrodotoxin (3 microM:), cadmium chloride (0.1 mM:), or the absence of Ca(2+) or Na(+) in the superfusion medium. Unexpectedly, higher concentrations of mecamylamine alone (1-50 microM:) 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 microM:) on 5-HT release was reduced by the muscarinic M(1) receptor agonist, McN-A-343 (100 microM:), but pirenzepine (0.005-1 microM:), which blocks M(1) receptors, alone increased 5-HT release. Hippocampal serotonergic neurones are known to possess both excitatory nicotinic receptors and inhibitory M(1) 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 microM:) 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.

subject areas

  • Animals
  • Calcium
  • Calcium Channel Blockers
  • Carrier Proteins
  • Dose-Response Relationship, Drug
  • Hippocampus
  • In Vitro Techniques
  • Male
  • Mecamylamine
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Nicotine
  • Nicotinic Agonists
  • Nicotinic Antagonists
  • Paroxetine
  • Rats
  • Rats, Inbred Strains
  • Receptor, Muscarinic M1
  • Receptors, GABA-A
  • Receptors, Glutamate
  • Receptors, Muscarinic
  • Receptors, Nicotinic
  • Serotonin
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Uptake Inhibitors
  • Tetrodotoxin
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Research

keywords

  • 5-hydroxytryptamine
  • McN-A-343
  • dorsal hippocampus
  • mecamylamine
  • nicotine
  • paroxetine
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Identity

International Standard Serial Number (ISSN)

  • 0022-3042

Digital Object Identifier (DOI)

  • 10.1046/j.1471-4159.2000.0752409.x

PubMed ID

  • 11080192
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Additional Document Info

start page

  • 2409

end page

  • 2414

volume

  • 75

issue

  • 6

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