Cited by 101Nicotinic Acetylcholine Receptors StudyNeuroscience and Neuropharmacology ResearchSmoking Behavior and Cessation

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

Kenny, Paul J., File, Sandra E., Neal, Michael J.·2000·Journal of Neurochemistry

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.

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Crossref · 10.1046/j.1471-4159.2000.0752409.x

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Authors
Kenny, P. J., File, S. E., & Neal, M. J.
Affiliations
King's College London (GB)
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2000-12
Volume
75
Issue
6
Pages
2409-2414
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
OpenAlex
W2029619668
Cited by
100
References
48
Citations by year
2025: 1 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 4 · 2017: 3 · 2016: 2 · 2015: 5 · 2014: 7 · 2013: 3 · 2012: 2
FWCI
1.69
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Neurochemistry (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
Keywords
nicotinic acetylcholine receptors, serotonin release, hippocampus, mecamylamine, M1 muscarinic receptor, McN-A-343, pirenzepine, serotonergic neurons, cholinergic modulation, inhibitory interneurons, nicotine
MeSH terms
Animals, Calcium, Calcium Channel Blockers, Carrier Proteins, Dose-Response Relationship, Drug, Hippocampus, Male, Mecamylamine, Membrane Glycoproteins, Nerve Tissue Proteins, Nicotine, Rats, Inbred Strains, Receptors, GABA-A, Receptors, Muscarinic, Receptors, Nicotinic, Serotonin, Tetrodotoxin, Selective Serotonin Reuptake Inhibitors, Paroxetine, Receptors, Glutamate, Nicotinic Agonists, Nicotinic Antagonists, Membrane Transport Proteins, Receptor, Muscarinic M1, Serotonin Plasma Membrane Transport Proteins, Rats, In Vitro Techniques

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