Decreased withdrawal symptoms but normal tolerance to nicotine in mice null for the α7 nicotinic acetylcholine receptor subunit
Open accessAbstract
Withdrawal symptoms are a major deterrent when people try to quit smoking. The alpha7 subunit of the neuronal nicotinic acetylcholine receptor (nAChR) is highly expressed in the brain, and has been suspected to play a major role in nicotine addiction. We studied the influence of alpha7-containing nAChRs on nicotine withdrawal and tolerance, in wild type mice and mice null for the alpha7 nAChR subunit (alpha7 -/-). For withdrawal experiments, animals were implanted with osmotic minipumps delivering nicotine for 13 days. A single intraperitoneal injection of the nAChR antagonists mecamylamine (MEC) or methyllycaconitine (MLA) was used to precipitate withdrawal. In wild type mice, both MEC- and MLA-precipitated somatic signs of withdrawal such as increased grooming, scratching and shaking. In alpha7 -/- mice, the somatic effects of MEC-precipitated nicotine withdrawal were significantly reduced. Interestingly, the presumed alpha7-specific antagonist MLA also precipitated withdrawal. Tolerance, which was measured as a decrease in nicotine-induced hypolocomotion after subchronic nicotine treatment, was normal in alpha7 -/- mice. Finally, because anxiety and withdrawal symptoms are highly correlated in humans, we studied anxiety-like behaviors in alpha7 -/- mice using a battery of anxiety-related tests. The behavior of alpha7 -/- mice was indistinguishable from that of control mice. Our results point to the alpha7 subunit as one of the players in nicotine withdrawal, but not in nicotine tolerance or basal anxiety-like behavior.
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α7 knockout mice show significantly fewer withdrawal symptoms immediately after mecamylamine-precipitated withdrawal.
“α7 null mice exhibit significantly reduced withdrawal symptoms immediately after precipitation of withdrawal by mecamylamine injection (Salas et al. 2007).”
From Nicotine Withdrawal (2015) · cites this paper as Salas et al. 2007
Not all withdrawal symptoms are mediated by β2* nAChRs; β4*, α5*, and α7 nAChRs, but not β2* nAChRs, contribute to somatic withdrawal symptoms.
“not all withdrawal symptoms are mediated by β2* nAChRs; for example, β4*, α5*, and α7 nAChRs, but not β2* nAChRs, contribute to somatic withdrawal symptoms (Jackson et al., 2008; Salas et al., 2007; Salas et al., 2004).”
From The duration of nicotine withdrawal-associated deficits in contextual fear conditioning parallels changes in hippocampal high affinity nicotinic acetylcholine receptor upregulation (2012) · cites this paper as Salas et al., 2007
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- Authors
- Salas, R., Main, A., Gangitano, D., & De Biasi, M.
- Affiliations
- Baylor College of Medicine (US)
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2007-12
- Volume
- 53
- Issue
- 7
- Pages
- 863-869
- ISSN
- 0028-3908 (ISSN-L)
- PMC
- PMC2149846
- OpenAlex
- W2066097877
- Cited by
- 76
- References
- 48
- Citations by year
- 2025: 3 · 2022: 2 · 2021: 2 · 2020: 2 · 2018: 2 · 2017: 5 · 2016: 3 · 2015: 9 · 2014: 6 · 2013: 8 · 2012: 6
- FWCI
- 2.91
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Drug Abuse (DA017173, R01DA017173)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- alpha7 nicotinic acetylcholine receptor, nicotine withdrawal, nicotine tolerance, nicotine dependence, mecamylamine, methyllycaconitine, anxiety-like behavior, knockout mice, smoking cessation
- MeSH terms
- Aconitine, Analysis of Variance, Anesthetics, Local, Animals, Behavior, Animal, Cocaine, Disease Models, Animal, Drug Tolerance, Exploratory Behavior, Female, Male, Mecamylamine, Mice, Inbred C57BL, Receptors, Nicotinic, Substance Withdrawal Syndrome, Mice, Knockout, Nicotinic Antagonists, Maze Learning, Mice, alpha7 Nicotinic Acetylcholine Receptor
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