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.

Spatial learning in Long-Evans Hooded rats and C57BL/6J mice: different strategies for different performance.

Spatial learning abilities of rodents have been extensively used to explore the management of a wide range of cognitive and emotional processes such as learning, memory, attention and anxiety. Knowledge about the organization and processing of spatial learning has mainly been obtained in rats. Due to increasing generation of genetically modified mice, cognitive abilities of mice are now extensively tested. The present paper aimed at comparing spatial representation, learning and strategies in C57BL/6J mice and Long-Evans Hooded rats when subjected to the same spatial learning paradigm, i.e. learning a food location in a crossmaze. We also analyzed the influence of environmental richness on learning modalities in both species. Our results showed that rats and mice could exhibit similar spatial learning abilities in some circumstances. However, Long-Evans rats and C57BL/6J mice may set up different strategies depending on the availability of visual information within the environment. Rats' learning strategies mainly relied on distant visual cues and seemed more efficient than those used by mice as they needed less time than mice to solve the task. We emphasize that the strategies of mice are less robust and flexible than the ones set up by rats. Finally, the richness of the environment was shown to affect speed and quality of spatial learning in both species.

Long-term effects of chronic nicotine exposure on brain nicotinic receptors.

Chronic nicotine exposure results in long-term homeostatic regulation of nicotinic acetylcholine receptors (nAChRs) that play a key role in the adaptative cellular processes leading to addiction. However, the relative contribution of the different nAChR subunits in this process is unclear. Using genetically modified mice and pharmacological manipulations, we provide behavioral, electrophysiological, and pharmacological evidence for a long-term mechanism by which chronic nicotine triggers opposing processes differentially mediated by beta2*- vs. alpha7*nAChRs. These data offer previously undescribed insights into the understanding of nicotine addiction and the treatment of several human pathologies by nicotine-like agents chronically acting on beta2*- or alpha7*nAChRs.

Long-term exposure to nicotine modulates the level and activity of acetylcholine receptors in white blood cells of smokers and model mice.

Long-term consumption of tobacco by smokers causes addiction and increases the level of neuronal nicotinic acetylcholine receptors (nAChRs) in the brain, a phenomenon known as up-regulation. Here, we show that up-regulation of specific nAChR subunits takes place in white blood cells (WBCs) of smokers and mice subjected to long-term administration of nicotine. The basal level of alpha-bungarotoxin binding site, which corresponds to the homomeric alpha7 nAChR subtype, was not affected in WBCs of both smokers and mice administered nicotine. In contrast, epibatidine (EB) binding sites, which correspond to heteromeric nAChR subtypes, were detected in WBCs of smokers but not in WBCs of nonsmokers. The number of EB binding sites significantly decreased after incubation of the smokers' WBCs for 3 days in nicotine-free culture medium. In WBCs of wild-type mice, basal level of EB binding sites was detected before nicotine administration. This basal level is reduced by approximately 60% in knockout mice lacking the genes encoding either the beta2 or the alpha4 receptor subunits. Additional analysis of knockout mice revealed that the remaining approximately 40% do not undergo up-regulation, indicating that the alpha4/beta2 subunits comprise the up-regulated nAChRs. We further found that upregulation in mouse WBCs is accompanied by a significant decrease in the capacity of the up-regulated receptor channels to convey calcium ions. The phenomenon of nAChR up-regulation in WBCs provides a simple tool to evaluate and study tobacco addiction.