Nicotinic acetylcholine receptor antagonist effect of fluoxetine in rat hippocampal slices
Abstract
We compared the effect of mecamylamine and fluoxetine on the hippocampal noradrenaline (NA) release evoked by nicotine in vitro. Nicotine (100 microM) increased the basal release of [3H]NA from rat hippocampal slices. This effect was blocked by the potent nicotinic antagonist mecamylamine in a dose-dependent manner (IC50 = 0.19 microM). The selective serotonin reuptake inhibitor (SSRI) fluoxetine also antagonised the response to nicotine in a dose-dependent manner with a similar strength (IC50 = 0.57 microM). Our data indicate that fluoxetine has nicotinic acetylcholine receptor antagonist effect in the central nervous system. The possible clinical significance of this finding is discussed.
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Antidepressant drugs behave as noncompetitive antagonists at nicotinic receptors across cellular, physiological, and behavioral measures.
“These drugs, including tricyclic antidepressants, selective serotonin reuptake inhibitors, and norepinephrine reuptake inhibitors, have been shown to act as noncompetitive nicotinic receptor (nAChR) antagonists on the cellular, physiologic, and behavioral level (Hennings et al., 1997;Fryer and Lukas, 1999;Lo ´pez-Valde ´s and García-Colunga, 2001).”
From Nicotinic Partial Agonists Varenicline and Sazetidine-A Have Differential Effects on Affective Behavior (2010) · cites this paper as Hennings et al., 1997
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- Authors
- Hennings, E. C. P., Kiss, J. P., & Vizi, E. S.
- Affiliations
- HUN-REN Institute of Experimental Medicine (HU)
- Corresponding author
- Vizi, E.Sylvester
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 1997-06
- Volume
- 759
- Issue
- 2
- Pages
- 292-294
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2033899006
- Cited by
- 55
- References
- 18
- Citations by year
- 2019: 2 · 2018: 3 · 2016: 2 · 2015: 1 · 2014: 2 · 2013: 1 · 2012: 1
- FWCI
- 1.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (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, fluoxetine, mecamylamine, noradrenaline release, nicotine, hippocampus, selective serotonin reuptake inhibitors, off-target effects
- MeSH terms
- Animals, Dose-Response Relationship, Drug, Fluoxetine, Hippocampus, Male, Mecamylamine, Rats, Wistar, Nicotinic Antagonists, Rats
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