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: 6535677
• 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/6535677
• 关键词: brain circulation; brain imaging /visualization /scanning; brain mapping; cardiovascular pharmacology; clinical research; cognition; drug /alcohol abstinence; human subject; memory; neuropharmacology; nicotine; nicotine replacement; performance; positron emission tomography; psychopharmacology; 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 with nonsmokers. In the first study, we administered nicotine gum (0, 2, 4 mg) to nonsmokers during a single session. In the second study, we administered nicotine gum (0, 2, 4, 8 mg) to nonsmokers for 8 consecutive days. 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. The brain's response to a drug or cognitive test can be obtained from mapping studies in which measurement of regional cerebral blood flow (rCBF) via PET is used to infer function. In our first study, we measured cognitive activation during a working memory test in smokers, who abstained from smoking for 12 hours, and ex-smokers in two sessions, separated by one week. At one session, subjects received placebo gum, and at the other session, they received 4 mg nicotine gum before performing the memory test and the brain scan. The two-back test involved a series of letters presented individually, and target letters were those that matched a letter two back in the series. Compared to placebo, nicotine reduced errors on the two-back test in smokers, but had no effect on test performance in ex-smokers. The brain regions activated by the two-back test were consistent with those reported in the literature: dorsolateral prefrontal cortex, anterior cingulate gyrus, and inferior parietal cortex. However, in the placebo condition, rCBF activation in the ex-smokers predominated in the left hemisphere, and in smokers in the right hemisphere, suggesting differing cognitive strategies. When nicotine was administered, rCBF activation was enhanced in ex-smokers, but reduced in smokers, perhaps reflecting chronic tolerance.

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，我们与非吸烟者进行了两项研究。在第一项研究中，我们在一次会话中向非吸烟者施用了尼古丁口香糖（0、2、4 mg）。在第二项研究中，我们连续8天对非吸烟者施用了尼古丁胶（0、2、4、8 mg）。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。大脑对药物或认知测试的反应可以从映射研究中获得，在该研究中，通过PET测量区域脑血流（RCBF）用于推断功能。在我们的第一个研究中，我们在吸烟者的工作记忆测试中测量了认知激活，他们戒烟12小时，在两次疗程中进行了两次疗程的前吸烟者，分别为一周。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。两回合测试涉及一系列单独呈现的字母，而目标字母是匹配该系列中两个字母的字母。与安慰剂相比，尼古丁在吸烟者中的两位后测试中的错误减少了，但对前吸烟者的测试表现没有影响。两次后背试验激活的大脑区域与文献中报道的大脑区域是一致的：背外侧前额叶皮层，前扣带回回和下顶皮层。但是，在安慰剂条件下，前吸烟者的RCBF激活在左半球和右半球的吸烟者中占主导地位，这表明认知策略不同。当尼古丁施用时，在前吸烟者中会增强RCBF激活，但吸烟者降低，也许反映了慢性耐受性。