Nicotine addiction: the possible role of functional upregulation
Abstract
Upregulation of binding to nicotinic acetylcholine receptors (nAChRs) is observed in the brains of both smokers and animals chronically exposed to nicotine, although whether this in vivo change is accompanied by an increase in receptor function is unknown. In vitro recordings indicate that alpha4beta2- and alpha7-subtypes of nAChRs, which are the most abundant subtypes in the brain, are functionally upregulated following prolonged exposure to nicotine. The possible consequences of functional upregulation for nicotine addiction are discussed. Moreover, we propose a new paradigm that describes the unusual behavior of these neuronal nAChRs and helps to explain the effects of nicotine in the CNS and the diffuse effects of ACh.
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Upregulation of high-sensitivity nAChRs is, at least partially, the basis for tolerance, locomotor sensitization, and cognitive sensitization caused by chronic nicotine administration.
“But increasing evidence suggests that upregulation of high-sensitivity nAChRs is, at least partially, the basis for several key biological results of chronic nicotine administration: tolerance, locomotor sensitization, and cognitive sensitization (5,10–12).”
From Nicotine is a selective pharmacological chaperone of acetylcholine receptor number and stoichiometry. Implications for drug discovery (2009) · cites this paper as [10]
Long-term nicotine exposure produces a region-specific upregulation of b2-containing nAChRs.
“Long-term nicotine exposure produces a region-specific upregulation of b2-containing nAChRs.”
From Activation of α4β2*/α6β2* nicotinic receptors alleviates anxiety during nicotine withdrawal without upregulating nicotinic receptors (2014) · cites this paper as Buisson and Bertrand, 2002
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- Authors
- Buisson, B., & Bertrand, D.
- Affiliations
- University of Geneva (CH)
- Corresponding author
- Buisson, Bruno
- ORCID
- Bertrand, Daniel
- Venue
- Trends in Pharmacological Sciences
- Publisher
- Elsevier BV
- Published
- 2002-03
- Volume
- 23
- Issue
- 3
- Pages
- 130-136
- ISSN
- 0165-6147 (ISSN-L)
- OpenAlex
- W2042529247
- Cited by
- 254
- References
- 55
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 2 · 2023: 4 · 2022: 2 · 2021: 5 · 2020: 3 · 2019: 4 · 2018: 7 · 2017: 6 · 2016: 6 · 2015: 4 · 2014: 10 · 2013: 8 · 2012: 7
- FWCI
- 1.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Pharmacological Sciences (publishedVersion)
- PubMed (publishedVersion)
- 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
- nicotine dependence, nicotinic acetylcholine receptors, receptor up-regulation, alpha4beta2 nAChR, alpha7 nAChR, chronic nicotine exposure, receptor function, cholinergic system
- MeSH terms
- Animals, Binding Sites, Brain, Cells, Cultured, Humans, Neurons, Nicotine, Receptors, Nicotinic, Tobacco Use Disorder, Up-Regulation, Smoking Cessation
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