Cited by 668Nicotinic Acetylcholine Receptors StudyNeuroscience and Neuropharmacology ResearchSmoking Behavior and Cessation

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Abnormal avoidance learning in mice lacking functional high-affinity nicotine receptor in the brain

Picciotto, Marina R., Zoli, Michele, Léna, Clement, Bessis, Alain, Lallemand, Yvan, LeNovère, Nicolas, Vincent, Pierre, Pich, Emilio Merlo, Brûlet, Philippe, Changeux, Jean-Pierre·1995·Nature

DOI 10.1038/374065a0

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Abstract

Nicotine affects many aspects of behaviour including learning and memory through its interaction with neuronal nicotinic acetylcholine receptors (nAChR). Functional nAChRs are pentameric proteins containing at least one type of alpha-subunit and one type of beta-subunit. The involvement of a particular neuronal nicotinic subunit in pharmacology and behaviour was examined using gene targeting to mutate beta 2, the most widely expressed nAChR subunit in the central nervous system. We report here that high-affinity binding sites for nicotine are absent from the brains of mice homozygous for the beta 2-subunit mutation. Further, electrophysiological recording from brain slices reveals that thalamic neurons from these mice do not respond to nicotine application. Finally, behavioural tests demonstrate that nicotine no longer augments the performance of beta 2-1- mice on passive avoidance, a test of associative memory. Paradoxically, mutant mice are able to perform better than their non-mutant siblings on this task.

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Authors: Picciotto, M. R., Zoli, M., Léna, C., Bessis, A., Lallemand, Y., LeNovère, N., Vincent, P., Pich, E. M., Brûlet, P., & Changeux, J.-P.
Affiliations: Centre National de la Recherche Scientifique (FR)
ORCID: Picciotto, Marina R.
Bessis, Alain
Vincent, Pierre
Pich, Emilio Merlo
Changeux, Jean-Pierre
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 1995-03
Volume: 374
Issue: 6517
Pages: 65-67
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/374065a0
OpenAlex: W1996157865
Cited by: 668
References: 26
Citations by year: 2026: 2 · 2025: 4 · 2023: 9 · 2022: 27 · 2021: 8 · 2020: 15 · 2019: 12 · 2018: 10 · 2017: 12 · 2016: 17 · 2015: 16 · 2014: 18 · 2013: 20 · 2012: 27
FWCI: 10.67
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
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 › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
Keywords: nicotinic acetylcholine receptors, beta2 subunit, avoidance learning, passive avoidance, associative memory, thalamic neurons, nicotine binding, gene targeting
MeSH terms: Animals, Avoidance Learning, Base Sequence, Brain, Cell Line, DNA, Female, Homozygote, Hypothalamus, Male, Mice, Inbred C57BL, Mice, Inbred DBA, Molecular Sequence Data, Mutation, Nicotine, Receptors, Nicotinic, Patch-Clamp Techniques, Mice

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Abnormal avoidance learning in mice lacking functional high-affinity nicotine receptor in the brain

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