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

尼古丁改善了吸烟者和非吸烟者的持续注意力作为一种基本的认知功能。注意力表现受损的受试者尼古丁成瘾的风险增加。动物研究表明，尼古丁对注意力的影响是由a4 b2烟碱乙酰胆碱受体（nAchR）介导的。我们开发了一种用于人体体内a4 b2成像的新型正电子发射断层扫描（PET）示踪剂（2-[18 F] F-A85380）。在本提案中，我们将讨论以下议题：（1）吸烟者和非吸烟者在持续注意期间a4 b2 nAchR与表现和皮层激活的关系，（2）尼古丁激发对持续注意力任务期间的表现和大脑激活的影响，与非吸烟者的a4 b2 nAchR密度和分布有关，以及（3）以下-本研究旨在探讨吸烟者戒烟后持续性注意任务中a4 b2 nAchR的变化及其与操作和脑激活的关系。新型a4 b2 nAchR配体的应用将有助于提高对尼古丁对人类注意力影响的理解。

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.