The β2 but not α7 subunit of the nicotinic acetylcholine receptor is required for nicotine-conditioned place preference in mice
Abstract
Rationale Tobacco use is implicated in approximately 440,000 deaths per year, making it the leading cause of preventable death in the United States. Although it is generally recognized that tobacco use is correlated with a variety of health-related complications, many smokers are unsuccessful in their efforts to stop smoking using current cessation therapies. Objectives Given that nicotine is the addictive component of tobacco, successful smoking cessation therapies must address the various processes, including reward, which contribute to nicotine addiction. As such, determining the nicotinic receptor subtypes involved in nicotine reward is of utmost importance to understanding how nicotine addiction progresses. Methods Conditioned place preference (CPP) in three-chamber conditioning boxes was performed. For antagonist studies, drug was given on all conditioning sessions 10 min before nicotine or saline injection and placement in the boxes. Results We have demonstrated that a pretreatment with the alpha4beta2 subunit of the nicotinic acetylcholine receptor (nAChR) antagonist dihydro-beta-erythroidine (2.0 mg/kg, s.c.) blocked nicotine (0.5 mg/kg, s.c.) CPP in wild-type mice (C57BL/6 mice). In contrast, pretreatment with an antagonist of the alpha7 subunit of the nAChR, methyllycaconitine (MLA, 5.0 or 10.0 mg/kg, s.c.), had no effect on this behavior. Finally, we showed that mice lacking the beta2 subunit of the nAChR did not exhibit nicotine CPP while alpha7 knock-out mice di…
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β2*-nAChRs are a critical neural substrate mediating the effects of nicotine in brain.
“In recent years evidence has emerged that the β2*-nAChRs are a critical neural substrate mediating the effects of nicotine in brain.”
From β2-Nicotinic Acetylcholine Receptor Availability During Acute and Prolonged Abstinence From Tobacco Smoking (2009) · cites this paper as [23]
The β2-subunit has been linked primarily to the reinforcing effects of nicotine and combines with the α3-6 subunits.
“Notably, the β2-subunit has been linked primarily to the reinforcing effects of nicotine22, 83, 84 and combines with the α3-6 subunits.”
From β2-Nicotinic Acetylcholine Receptor Availability During Acute and Prolonged Abstinence From Tobacco Smoking (2009) · cites this paper as [83]
Knockout of the α7 subunit in mice does not affect nicotine place preference or acquisition of nicotine self-administration.
“Despite its contribution to nicotine-dependent plasticity in the VTA, knockout of the α7 subunit in mice does not affect nicotine place preference (Walters et al. 2006) or acquisition of nicotine self-administration (Pons et al. 2008).”
From Mechanisms of Nicotine Addiction (2021) · cites this paper as Walters et al. 2006
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- Authors
- Walters, C. L., Brown, S., Changeux, J.-P., Martin, B., & Damaj, M. I.
- Affiliations
- Virginia Commonwealth University (US)
- Institut Pasteur (FR)
- Corresponding author
- Walters, Carrie L.
- Venue
- Psychopharmacology
- Published
- 2006-01-14
- Volume
- 184
- Issue
- 3-4
- Pages
- 339-344
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W2142606268
- Cited by
- 206
- References
- 30
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 3 · 2023: 2 · 2022: 4 · 2021: 7 · 2020: 9 · 2019: 5 · 2018: 7 · 2017: 6 · 2016: 10 · 2015: 9 · 2014: 16 · 2013: 22 · 2012: 14
- FWCI
- 7.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- National Institutes of Health
- National Institute on Drug Abuse (DA 07027, R01DA012610, DA 05274, DA-12610, T32DA007027)
- 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 › Neurotransmitter Receptor Influence on Behavior
- Keywords
- nicotinic acetylcholine receptors, beta2 subunit, alpha7 subunit, nicotine reward, nicotine dependence, conditioned place preference, dihydro-beta-erythroidine, methyllycaconitine, tobacco use
- MeSH terms
- Aconitine, Animals, Choice Behavior, Conditioning, Psychological, Dihydro-beta-Erythroidine, Female, Heterozygote, Male, Mice, Inbred C57BL, Motivation, Premedication, Receptors, Nicotinic, Reinforcement Schedule, Social Environment, Tobacco Use Disorder, Mice, Knockout, Mice, alpha7 Nicotinic Acetylcholine Receptor
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