Cited by 225Nicotinic Acetylcholine Receptors StudyNeuroscience and Neuropharmacology ResearchSmoking Behavior and Cessation

Neuronal nicotinic acetylcholine receptor subunit knockout mice: physiological and behavioral phenotypes and possible clinical implications

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Picciotto, Marina R, Caldarone, Barbara J, Brunzell, Darlene H, Zachariou, Venetia, Stevens, Tanya R, King, Sarah L·2001·Pharmacology & Therapeutics

Abstract

Nicotinic acetylcholine receptors (nAChRs) in the muscle, autonomic ganglia, and brain are targets for pharmacologically administered nicotine. Several of the subunits that combine to form neuronal nicotinic receptors have been deleted by knockout or mutated by knockin in mice using homologous recombination. We will review the biochemical, pharmacological, anatomical, physiological, and behavioral phenotypes of mice with genetically altered neuronal nAChR subunits. Clinically relevant mutations in nAChR genes will also be discussed. In addition, some of the signal transduction pathways activated through nAChRs will be described in order to delineate the longer-term changes that might result from persistent activation or inactivation of nAChRs. Genetically manipulated mice have greatly increased our understanding of the subunit composition and physiological properties of nAChRs in vivo. In addition, these mice have provided a model system to determine the molecular basis for many of the pharmacological actions of nicotine on neurotransmitter release and behavior. Genetic manipulations in mice have also elucidated the role of nAChR subunits in various disease states, and suggest several avenues for drug development.

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Crossref · 10.1016/s0163-7258(01)00161-9

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  • Nicotinic receptors function as non-selective, excitatory cation channels.

    “Nicotinic receptors function as non-selective, excitatory cation channels (Changeux et al., 1998; Picciotto et al., 2001) and occur as homomeric or heteromeric assemblies of a large family of α- and β-subunits (α2-α7 and β2-β4; reviewed in (Picciotto et al., 2000)).”

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Authors
Picciotto, M. R., Caldarone, B. J., Brunzell, D. H., Zachariou, V., Stevens, T. R., & King, S. L.
Affiliations
Yale University (US)
Corresponding author
Picciotto, Marina R
Venue
Pharmacology & Therapeutics
Publisher
Elsevier BV
Published
2001-11
Volume
92
Issue
2-3
Pages
89-108
ISSN
0163-7258 (ISSN-L)
OpenAlex
W2053266420
Cited by
221
References
176
Citations by year
2026: 2 · 2025: 3 · 2024: 11 · 2023: 5 · 2022: 3 · 2021: 6 · 2020: 6 · 2019: 6 · 2018: 5 · 2017: 5 · 2016: 6 · 2015: 10 · 2014: 14 · 2013: 2 · 2012: 17
FWCI
0.62
Type
journal article
Language
en
Open access
Locations
  • Pharmacology & Therapeutics (publishedVersion)
  • PubMed (publishedVersion)
  • Figshare (submittedVersion, cc-by)
  • Sussex Research Online (University of Sussex) (submittedVersion)
Funders
  • National Institutes of Health
  • National Institute on Drug Abuse (DA 10455, DA84733, DA 00436)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
Keywords
neuronal nicotinic acetylcholine receptors, nicotine pharmacology, signal transduction, neurotransmitter release, behavioral phenotypes, physiological phenotypes, drug development
MeSH terms
Animals, Anxiety, Electrophysiology, Learning, Memory, Neurons, Nicotine, Phenotype, Receptors, Nicotinic, Signal Transduction, Point Mutation, Mice, Knockout, Nicotinic Agonists, Mice

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