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Picciotto, MR, Zoli, M, Léna, C, Bessis, A, Lallemand, Y, Le Novère, N, Vincent, P, Pich, EM, Brûlet, P and Changeux, JP (1995) Abnormal avoidance learning in mice lacking functional high-affinity nicotine receptor in the brain. Nature 374:65-7
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.
Animals; Avoidance Learning/drug effects; Base Sequence; Brain/drug effects; Brain/metabolism; Cell Line; DNA; Female; Homozygote; Hypothalamus/metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Molecular Sequence Data; Mutation; Nicotine/pharmacology; Patch-Clamp Techniques; Receptors, Nicotinic/deficiency; Receptors, Nicotinic/genetics; Receptors, Nicotinic/metabolism