Cognition, Tobacco Smoke and Nicotinic Receptor Occupancy

描述（申请人提供）：认知、烟草烟雾和尼古丁受体占据吸烟对认知有有益的影响。在某些情况下，吸烟可以提高认知能力，而在另一些情况下，它可以逆转吸烟剥夺带来的缺陷。吸烟的许多认知增强作用归因于尼古丁对尼古丁乙酰胆碱受体（nAChR）的药理作用。尼古丁可以改善工作记忆任务、集中和持续注意力的运动反应测试以及识别记忆的表现。除尼古丁外，烟草烟雾还含有大约4000种额外的化合物，其中许多具有药理活性，可能导致吸烟对认知的影响。尼古丁和吸烟对认知的影响还没有被描述出来。此外，脑尼古丁乙酰胆碱受体（nAChR）的尼古丁占用程度与认知表现的关系尚不清楚。在本研究中，我们拟探讨烟草烟雾、去硝化烟草烟雾和尼古丁对吸烟者在积极吸烟时注意力、学习、记忆、信息处理速度和执行功能等认知任务的影响；禁欲12 ~ 24 h；戒烟7天后，吸烟含尼古丁香烟后；使用尼古丁吸入器后的去尼古丁香烟。认知表现与脑（32-nAChR）数量以及向皮质和皮质下脑区递送的尼古丁量之间的关系将使用[123I] 5-IA-85380和SPECT进行测量。这些探索性研究将描述尼古丁与去尼古丁化烟草烟雾对急性戒烟者认知表现的作用。此外，它们将提供关于尼古丁与p2-nAChR的相互作用以及与认知表现改善的关系的关键信息。

DESCRIPTION (provided by applicant): Cognition, Tobacco Smoke and Nicotinic Receptor Occupancy Tobacco smoking has beneficial effects on cognition. In some cases smoking improves cognitive performance and in others it reverses deficits brought on by smoking deprivation. Many of the cognitive enhancing effects of smoking have been attributed to the pharmacological actions of nicotine on nicotinic acetylcholine receptors (nAChR). Nicotine improves performance on working memory tasks, motor response tests of focused and sustained attention and recognition memory. In addition to nicotine, tobacco smoke includes approximately 4000 additional compounds, of which many are pharmacologically active and may contribute to the effects of smoking on cognition. The cognitive effects of nicotine versus tobacco smoke have not yet been delineated. Moreover it is not clear how the degree of nicotine occupancy of brain nicotinic acetylcholine receptors (nAChR ) is correlated with cognitive performance. In the present study we propose to explore the effects of tobacco smoke, denicotinized tobacco smoke and nicotine on performance on cognitive tasks of attention, learning, memory, speed of information processing and executive functions in smokers while they are actively smoking; after 12 -24 h abstinence; after 7 days abstinence and after smoking a nicotine-containing cigarette; a de-nicotinized cigarette and after using the nicotine inhaler. The relationship between cognitive performance and the number of brain (32-nAChR and the amount of nicotine delivered to cortical and subcortical brain areas will be measured using [123I] 5-IA-85380 and SPECT. These exploratory studies will delineate the role of nicotine versus denicotinized tobacco smoke on cognitive performance in acutely abstinent smokers. In addition they will provide critical information about the interaction of nicotine with p2-nAChR and the relationship to improvements in cognitive performance.