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

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Abstract

NICOTINE affects many aspects of behaviour including learning and memory1,2 through its interaction with neuronal nicotinic acetylcholine receptors (nAChR). Functional nAChRs are pentameric proteins containing at least one type of a-subunit and one type of p-subunit3–5. The involvement of a particular neuronal nicotinic subunit in pharmacology and behaviour was examined using gene targeting to mutate β2, the most widely expressed nAChR subunit in the central nervous system6–8. We report here that high-affinity binding sites for nicotine are absent from the brains of mice homozygous for the β2-subunit mutation. Further, electrophysiological recording from brain slices reveals that thalamic neurons from these mice do not respond to nicotine application. Finally, behav- ioural tests demonstrate that nicotine no longer augments the performance of β2-/-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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Author notes

  1. Yvan Lallemand and Philippe Brûlet: Unite d'Embryologie Moléculaire de L'lnstitut Pasteur, EPS 67, Paris, France

  2. Pierre Vincent: Department of Neurobiology, Glaxo Institute for Molecular Biology, Geneva Switzerland

Authors and Affiliations

  1. CNRS UA D1284 Neurobiologie Moléculaire, Institut Pasteur, 28 rue du Dr Roux, 75724, Paris, Cédex 15, France

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

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  1. Marina R. Picciotto
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  2. Michele Zoli
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  3. Clement Léna
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  4. Alain Bessis
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  5. Yvan Lallemand
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  6. Nicolas LeNovère
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  7. Pierre Vincent
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  8. Emilio Merlo Pich
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  9. Philippe Brûlet
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  10. Jean-Pierre Changeux
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Picciotto, M., Zoli, M., Léna, C. et al. Abnormal avoidance learning in mice lacking functional high-affinity nicotine receptor in the brain. Nature 374, 65–67 (1995). https://doi.org/10.1038/374065a0

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