Chronic nicotine exposure has dissociable behavioural effects on control and beta2-/- mice

Nicotine exerts beneficial effects on various neurological and psychiatric pathologies, yet its effects on cognitive performance remain unclear. Mice lacking the beta2 subunit of the nicotinic receptor (beta2-/-) show characteristic deficits in executive functions and are suggested as reliable animal models for some specific endophenotypes of human pathologies, notably ADHD. We use beta2-/- and their controls to investigate the consequences of chronic nicotine exposure on cognitive behaviour. We show that in control mice, this treatment elicits somewhat slight effects, particularly affecting nocturnal activity and self-grooming. By contrast, in beta2-/- mice, chronic nicotine treatment had restorative effects on exploratory behaviour in the open-field and affected rearing, but did not modify motor functions. We confirmed that beta2-/- mice exhibit impaired exploratory and social behaviour, and further demonstrated their nocturnal hyperactivity. These data support the proposal that beta2-/- mice represent a relevant model for cognitive disorders in humans and that nicotine administered chronically at low dose may relieve some of these.