Cited by 77Nicotinic Acetylcholine Receptors StudySmoking Behavior and CessationNeuroscience and Neuropharmacology Research

Decreased withdrawal symptoms but normal tolerance to nicotine in mice null for the α7 nicotinic acetylcholine receptor subunit

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Salas, Ramiro, Main, Adam, Gangitano, David, De Biasi, Mariella·2007·Neuropharmacology

Abstract

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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Crossref · 10.1016/j.neuropharm.2007.08.017

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  1. Booker TK, Tritto T, Colman J, Cui C, Collins ACFHS. The 20th Neuropharmacology Conference. Vol. 1. Elsevier Science; New Orleans: 2000. Beta3 subunits in regulation of anxiety: analysis of beta3 null mutant mice; p. 65. [Google Scholar]

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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)
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
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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