The role of a4b2 nicotinic acetylcholine receptors in sustained attention: effects in smokers and non-smokers

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Sustained attention as a basic cognitive function is improved by nicotine in smokers and non-smokers. Subjects with impaired attentional performance are at increased risk for nicotine addiction. Animal studies suggest that the effect of nicotine on attention is mediated by the a4b2 nicotinic acetylcholine receptor (nAchR). We developed a novel positron emission tomography (PET) tracer for a4b2 imaging in humans in vivo (2-[18F] F-A85380). In the present proposal, we will address the following topics: (1) relationship of the a4b2 nAchR with performance and cortical activation during sustained attention in smokers and non-smokers, (2) effect of nicotine challenge on performance and cerebral activation during a sustained attention task in relation to the a4b2 nAchR density and distribution in non-smokers and (3) follow-up study on changes of the a4b2 nAchR and performance and cerebral activation in a sustained attention task in smokers following smoking cessation. The application of the novel a4b2 nAchR ligand will help to improve the understanding of nicotine effects on attention in humans.