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Evidence for a Complex Influence of Nicotinic Acetylcholine Receptors on Hippocampal Serotonin Release
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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“both nicotine and the nicotinic antagonist mecamylamine can increase serotonin release in the hippocampus (Kenny et al., 2000)”
From Mood and anxiety regulation by nicotinic acetylcholine receptors: A potential pathway to modulate aggression and related behavioral states (2015) · cites this paper as Kenny et al., 2000
In the citing paper
“both chronic nicotine and the nicotinic antagonist mecamylamine can facilitate serotonin transmission in the hippocampus, while the effects of monoamine depletion can be partially reversed by nicotine administration and can lead to changes in anxiety-like behavior in the elevated plus maze (File et al., 2000a; File et al., 2000b; Fu et al., 1998; Kenny et al., 2000)”
From Mood and anxiety regulation by nicotinic acetylcholine receptors: A potential pathway to modulate aggression and related behavioral states (2015) · cites this paper as Kenny et al., 2000
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Metadata
- Authors
- Kenny, P. J., File, S. E., & Neal, M. J.
- Affiliations
- King's College London (GB)
- ORCID
- Kenny, Paul J.
- 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 › Public Health, Environmental and Occupational Health › 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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