Chronic Nicotine Exposure has Dissociable Behavioural Effects on Control and Beta2−/− Mice

Abstract

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.

Brain activation by short-term nicotine exposure in anesthetized wild-type and beta2-nicotinic receptors knockout mice: a BOLD fMRI study

“…Nicotinemediated co-activation has been studied only in slice preparations and therefore refers to local circuits (Le Magueresse et al 2006). Our present data reinforce and complete our previous behavioral and electrophysiological data (Besson et al 2007(Besson et al , 2008 showing that α7 receptors contribute to such nicotine-mediated co-activation. Using viral vector-mediated restoration, we demonstrated previously that β2-containing receptors are involved in the acetylcholine-mediated co-activation in the absence of nicotine (Maskos et al 2005).…”

Behavioral Sequence Analysis Reveals a Novel Role for ß2* Nicotinic Receptors in Exploration

“…Accordingly, increased probability of center engagement after scanning may be viewed as caused by a reduction of anxiety (Figure 8). Yet, WT and ß2−/− mice have similar levels of anxiety [4],[31], furthermore the parallel evolution of CA → CI probability of transition suggest that reduction of anxiety with time is similar in both strain. The observation that the structure of the displacement is modified in ß2−/− mice and that this modification targets “scanning” as a key feature in the organization of behavior suggests instead a modification of information gathering and of the risk/gain optimization.…”

Prefrontal nicotinic receptors control novel social interaction between mice

“…In the behavioral paradigm used here, mice previously deprived of social interaction are exposed to an unknown conspecific in a novel environment (6,18). Isolated mice are thus placed in a situation in which they have to select between exploring the novel arena and seeking social contact.…”