Cited by 131Nicotinic Acetylcholine Receptors StudySmoking Behavior and CessationNeuroscience and Neuropharmacology Research

Subtypes of nicotinic acetylcholine receptors in nicotine reward, dependence, and withdrawal: evidence from genetically modified mice

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Fowler, Christie D., Arends, Michael A., Kenny, Paul J.·2008·Behavioural Pharmacology

Abstract

Neuronal nicotinic acetylcholine receptors (nAChRs) can regulate the activity of many neurotransmitter pathways throughout the central nervous system and are considered to be important modulators of cognition and emotion. nAChRs are also the primary site of action in the brain for nicotine, the major addictive component of tobacco smoke. nAChRs consist of five membrane-spanning subunits (alpha and beta isoforms) that can associate in various combinations to form functional nAChR ion channels. Owing to a dearth of nAChR subtype-selective ligands, the precise subunit composition of the nAChRs that regulate the rewarding effects of nicotine and the development of nicotine dependence are unknown. The advent of mice with genetic nAChR subunit modifications, however, has provided a useful experimental approach to assess the contribution of individual subunits in vivo. Here, we review data generated from nAChR subunit knockout and genetically modified mice supporting a role for discrete nAChR subunits in nicotine reinforcement and dependence processes. Importantly, the rates of tobacco dependence are far higher in patients suffering from comorbid psychiatric illnesses compared with the general population, which may at least partly reflect disease-associated alterations in nAChR signaling. An understanding of the role of nAChRs in psychiatric disorders associated with high rates of tobacco addiction, therefore, may reveal novel insights into mechanisms of nicotine dependence. Thus, we also briefly review data generated from genetically modified mice to support a role for discrete nAChR subunits in anxiety disorders, depression, and schizophrenia.

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  1. American Psychiatric Association 1994 Book Diagnostic and Statistical Manual of Mental Disorders 4th Washington, DC American Psychiatric Press

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Authors
Fowler, C. D., Arends, M. A., & Kenny, P. J.
Affiliations
Scripps Research Institute (US)
Corresponding author
Kenny, Paul J.
Venue
Behavioural Pharmacology
Published
2008-09
Volume
19
Issue
5-6
Pages
461-484
ISSN
0955-8810 (ISSN-L)
OpenAlex
W2091328294
Cited by
131
References
357
Citations by year
2026: 2 · 2025: 2 · 2024: 8 · 2023: 3 · 2022: 7 · 2021: 4 · 2020: 6 · 2019: 2 · 2018: 6 · 2017: 8 · 2016: 8 · 2015: 11 · 2014: 13 · 2013: 8 · 2012: 16
FWCI
0.70
Type
journal article
Language
en
Open access
Locations
  • Behavioural Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute on Drug Abuse (DA020686, R01DA020686, R37DA020686)
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
nicotinic acetylcholine receptors, nicotine reward, nicotine dependence, nicotine withdrawal, genetically modified mice, alpha and beta subunits, tobacco dependence, psychiatric comorbidity, anxiety disorders, depression, schizophrenia
MeSH terms
Animals, Anxiety Disorders, Arousal, Depressive Disorder, Genotype, Humans, Nicotine, Phenotype, Receptors, Nicotinic, Reward, Schizophrenia, Substance Withdrawal Syndrome, Tobacco Use Disorder, Signal Transduction, Comorbidity, Mice, Knockout, Animals, Genetically Modified, Mice, alpha7 Nicotinic Acetylcholine Receptor

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