Genetic dissociation of two behaviors associated with nicotine addiction: Beta-2 containing nicotinic receptors are involved in nicotine reinforcement but not in withdrawal syndrome
Abstract
Rationale Nicotine addiction is characterized by two distinct behaviors, chronic compulsive self-administration and the induction of a withdrawal syndrome upon cessation of nicotine consumption. Objective To examine if these two processes rely on beta2-containing nicotinic receptors--beta2*nAChRs--we analyzed the behavior of mice lacking these receptors in the two situations. Results First, we showed that, in contrast to wild-type (WT) mice, beta2-knockout (beta2-/-) mice exhibit no intra-ventral tegmental area (VTA) nicotine self-administration, whereas their ability to self-administer morphine is intact. However, beta2-/- mice showed some sensitivity to locomotor effects of nicotine, implying an effect of the drug on other nicotinic subtypes. Then, we observed that beta2-/- mice exhibited a normal nicotine withdrawal syndrome, i.e., increased levels of rearing and jumping upon precipitated withdrawal. Thus, the beta2*nAChRs are not involved in the behaviors induced by cessation of nicotine consumption. Conclusion Taken together, the present data demonstrated a genetic dissociation of two distinct behavioral patterns associated with nicotine addiction. They further suggested that independent molecular mechanisms underlie these two aspects, offering the possibility of controlling them separately.
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The β2*-subtype does not play a critical role in the physical symptoms of nicotine withdrawal.
“This is consistent with the preclinical literature suggesting that the β2*-subtype does not play a critical role in the physical symptoms of nicotine withdrawal33, 76.”
From β2-Nicotinic Acetylcholine Receptor Availability During Acute and Prolonged Abstinence From Tobacco Smoking (2009) · cites this paper as [33]
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- Authors
- Besson, M., David, V., Suarez, S., Cormier, A., Cazala, P., Changeux, J.-P., & Granon, S.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Granon, S.
- Venue
- Psychopharmacology
- Published
- 2006-06-03
- Volume
- 187
- Issue
- 2
- Pages
- 189-199
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W2034426909
- Cited by
- 73
- References
- 53
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 2 · 2020: 3 · 2019: 2 · 2016: 3 · 2015: 7 · 2014: 4 · 2013: 5 · 2012: 1
- FWCI
- 4.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Centre National de la Recherche Scientifique
- 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
- nicotine dependence, nicotine self-administration, nicotine withdrawal, ventral tegmental area, morphine self-administration
- MeSH terms
- Animals, Male, Mice, Inbred C57BL, Morphine, Nicotine, Receptors, Nicotinic, Reinforcement, Psychology, Self Administration, Substance Withdrawal Syndrome, Tobacco Use Disorder, Ventral Tegmental Area, Mice, Knockout, Mice
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