Effects Of Nicotine And Smoking On Cognitive Function

尼古丁和吸烟对认知功能的影响

• 批准号: 6830649
• 负责人: Stephen J. Heishman
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON DRUG ABUSE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6830649
• 关键词: behavioral /social science research tag; brain imaging /visualization /scanning; brain morphology; clinical research; clinical trials; cognition; drug withdrawal; functional magnetic resonance imaging; human subject; memory; nicotine; nicotine replacement; performance; positron emission tomography; psychological tests; reinforcer; smoking; tobacco abuse

Many cigarette smokers report that smoking helps them stay alert and improves their concentration. But does tobacco use confer a general cognitive advantage to smokers or do smokers perceive a boost in performance because nicotine can reverse transient cognitive deficits due to brief (between cigarettes) or prolonged (overnight) periods of tobacco abstinence? Our research in this area has attempted to answer this fundamental question: how does smoking or nicotine affect human cognition? In several studies, we demonstrated that tobacco abstinence can impair cognitive functioning and that, in general, smoking or nicotine reverses such deficits to smoking baseline levels. These data strongly suggest that this is one mechanism that functions to maintain smoking in nicotine-dependent individuals. However, determining whether smoking or nicotine can truly enhance cognition, rather than simply provide withdrawal relief, can be difficult in smokers. Thus, we conducted two studies in which we administered nicotine gum to nonsmokers. The data from both studies were consistent in finding no cognitive enhancing effects of nicotine. The data do not support the hypothesis that nicotine-induced cognitive enhancement contributes to the reinforcing effects of tobacco use during the early stages of nicotine dependence. We have also begun to explore the brain regions activated during performance of cognitive tests and the effect of nicotine on brain activation. In one study, we used PET imaging to measure cognitive activation during a working memory test in smokers, who abstained from smoking for 12 hours, and ex-smokers. At one session, subjects received placebo gum, and at another session, they received 4 mg nicotine gum before performing the memory test and the brain scan. Compared to placebo, nicotine reduced errors on the memory test in smokers, but had no effect on test performance in ex-smokers. The brain regions activated by the memory test were consistent with those reported in the literature: dorsolateral prefrontal cortex, anterior cingulate gyrus, and inferior parietal cortex. When nicotine was administered, brain activation was enhanced in ex-smokers, but reduced in smokers, perhaps reflecting chronic tolerance. In an ongoing study, we are using functional magnetic resonance imaging (fMRI) to investigate changes in brain activity and cognitive abilities during 8 days of tobacco abstinence, continued smoking, or smoking denicotinized cigarettes. This will allow us to determine whether withdrawal effects are due to the absence of tobacco (abstinence condition) or the absence of nicotine (denicotinized cigarette condition).

许多吸烟者报告说，吸烟有助于他们保持警惕并提高注意力。但是，烟草使用是否赋予吸烟者的一般认知优势，或者吸烟者认为效果会提高性能，因为尼古丁可以由于短暂的（在香烟之间）或延长（过夜）烟草的戒烟而逆转短暂的认知缺陷？我们在该领域的研究试图回答这个基本问题：吸烟或尼古丁如何影响人类认知？在几项研究中，我们证明戒烟会损害认知功能，通常，吸烟或尼古丁将这种赤字逆转为吸烟基线水平。这些数据强烈表明，这是一种在依赖尼古丁依赖性个体中吸烟的机制。但是，确定吸烟或尼古丁是否可以真正增强认知，而不是简单地提供戒烟，这在吸烟者中可能很难。因此，我们进行了两项研究，在其中将尼古丁口香糖用于非吸烟者。两项研究的数据在没有发现尼古丁的认知增强作用方面是一致的。数据不支持以下假设：尼古丁诱导的认知增强有助于烟碱依赖性早期烟草使用的增强作用。我们还开始探索在认知测试的性能过程中激活的大脑区域以及尼古丁对脑激活的影响。在一项研究中，我们使用PET成像来测量吸烟者的工作记忆测试期间的认知激活，他们戒烟了12小时，并且前吸烟者。在一次会议上，受试者接受了安慰剂口香糖，在另一届会议上，他们在进行记忆测试和大脑扫描之前收到了4毫克尼古丁口香糖。与安慰剂相比，尼古丁在吸烟者的记忆测试中减少了错误，但对前吸烟者的测试表现没有影响。通过记忆测试激活的大脑区域与文献中报道的大脑区域一致：背外侧前额叶皮层，前扣带回回和下顶皮层。当尼古丁施用时，前吸烟者的大脑激活得到了增强，但吸烟者的降低，可能反映了慢性耐受性。在一项正在进行的研究中，我们正在使用功能磁共振成像（fMRI）来研究烟草禁欲的8天，持续吸烟或吸烟否认的香烟的大脑活动和认知能力的变化。这将使我们能够确定戒断效应是由于缺乏烟草（禁欲条件）还是缺乏尼古丁（否认香烟状况）。