ABNORMAL AVOIDANCE-LEARNING IN MICE LACKING FUNCTIONAL HIGH-AFFINITY NICOTINE RECEPTOR IN THE BRAIN

NICOTINE affects many aspects of behaviour including learning and memo ry(1,2) through its interaction with neuronal nicotinic acetylcholine receptors (nAChR). Functional nAChRs are pentameric proteins containin g at least one type of alpha-subunit and one type of beta-subunit(3-5) . The involvement of a particular neuronal nicotinic subunit in pharma cology and behaviour was examined using gene targeting to mutate beta 2, the most widely expressed nAChR subunit in the central nervous syst em(6-8). We report here that high-affinity binding sites for nicotine are absent from the brains of mice homozygous for the beta 2-subunit m utation. Further, electrophysiological recording from brain slices rev eals that thalamic neurons from these mice do not respond to nicotine application. Finally, bebavioural tests demonstrate that nicotine no l onger augments the performance of beta 2(-/-) mice on passive avoidanc e, a test of associative memory. Paradoxically, mutant mice are able t o perform better than their non-mutant siblings on this task.