Beta2-containing neuronal nicotinic receptors as major actors in the flexible choice between conflicting motivations.

Beside a critical role in nicotine addiction, the role of nicotinic receptors in cognitive or emotional processes remains difficult to elucidate, mostly because of a lack of specificity of compounds and because they up or down regulate easily. Using knockout mice may be one key to elucidate the role of nicotinic receptors stimulated by their endogenous ligand acetylcholine. We and others have previously explored the behaviour of mice knockout for the beta2-subunit containing nicotinic receptor - β2*nAChRs - β2(-/-) mice. These mice exhibit a particular kind of hyperactive locomotion, with profound deficits in cognitive and social interaction tasks, only when they have to show flexible choices. We wonder here whether the latter is due to a lack of motor control - i.e. motor impulsivity, a lack of estimation of reward value - i.e. cognitive impulsivity, and/or a lack of appropriate ranking or choice between different motivations. We designed behavioural tasks allowing the study of these distinct processes in mice. Our current results highlight the important role of β2*nAChRs in flexible behaviours in conflicting situations, such as social contact, spatial exploration and food consumption. They also show that the cognitive deficits exhibited by β2(-/-) mice cannot be explained by impaired inhibitory behaviours. Although social cognition is considerably enriched in humans as compared to rodents, we provide here novel data for the neurobiology of flexible social behaviours that could ultimately be useful for humans. Indeed, the ability to show flexible behaviours and to display adapted social interactions is profoundly impaired in a myriad of psychiatric disorders.