Neurobiology of Nicotine and Non-nicotine Components of Tobacco Addiction

描述(由申请人提供)：新出现的证据强调了非尼古丁、感觉运动因素(例如，味道、香味、手感)在香烟成瘾中的重要性。与静脉注射相比，吸烟者更喜欢去尼古丁香烟。尼古丁的脉冲，以及对吸烟感官方面的阻断，大大降低了吸烟的满意度和强化程度。此外，解决对烟草成瘾的非尼古丁成分依赖的新疗法已经显示出希望。尽管最近人们认识到香烟成瘾中的非尼古丁、感觉运动因素，但人们对烟草成瘾中尼古丁和非尼古丁成分的神经生物学基础知之甚少。因此，这项研究的广泛目标是通过系统地改变尼古丁和非尼古丁因子的给药方式，并使用功能磁共振成像测量它们对大脑功能的影响，来评估导致香烟成瘾的尼古丁和非尼古丁因子的神经生物学基础。在完全析因设计中，36名吸烟者将在24小时后接受成像：1)吸食去尼古丁香烟的尼古丁贴片，2)吸食去尼古丁香烟的安慰剂贴片，3)仅吸食尼古丁贴片，以及4)仅吸食安慰剂贴片。两项对尼古丁和非尼古丁因素不同敏感的任务将分别完成连续工作记忆任务(CWM)和线索反应任务(CR)。我们假设，戒烟(无论吸烟与否)将导致较差的CWM表现和左侧背外侧前额叶皮质(DlPFC)的激活；而戒烟和尼古丁将导致更大的戒烟诱导的渴望和皮质、边缘和纹状体区域网络的激活。自我报告的吸烟动机和其他吸烟相关因素的个体差异将预测尼古丁和非尼古丁因素对大脑功能的影响。此外，还将对36名不吸烟者的样本进行扫描，并检查吸烟者和不吸烟者群体的差异。这项研究的结果将为烟草依赖的神经生物学基础提供新的线索，并为理解烟草使用、戒烟和复发的个体差异提供一个框架。此外，它还将提供基础科学信息，帮助开发新的、可能更有效的治疗方法，解决吸烟中的尼古丁和非尼古丁成分。公共卫生相关性：在美国，吸烟是导致死亡和残疾的主要原因。人们越来越认识到，除了尼古丁之外，其他因素也会导致吸烟上瘾。这些因素既包括感官因素(味觉、气味)，也包括行为因素(吹气、手感)。更好地了解这些因素是如何影响大脑的，可以带来帮助吸烟者戒烟的新的、更有效的治疗方法。

DESCRIPTION (provided by applicant): Emerging evidence highlights the importance of non-nicotine, sensorimotor factors (e.g., taste, aroma, handling) in cigarette addiction. Smokers prefer denicotinized cigarettes over i.v. pulses of nicotine, and blockade of the sensory aspects of smoking significantly reduces smoking satisfaction and reinforcement. Moreover, new treatments that address dependence on non-nicotine components of tobacco addiction have shown promise. Despite recent appreciation of non-nicotine, sensorimotor factors in cigarette addiction, little is known about the neurobiological basis of nicotine versus non-nicotine components of tobacco addiction. Thus, the broad objective of this research is to evaluate the neurobiological basis of nicotine and non-nicotine factors underlying cigarette addiction by systematically varying administration of these factors and measuring their effects on brain function using fMRI. In a fully factorial design, thirty-six (36) smokers will undergo imaging following 24 hrs of: 1) nicotine patch + smoking denicotinized [denic] cigarettes, 2) placebo patch + smoking denic cigarettes, 3) nicotine patch only, and 4) placebo patch only. Two tasks differentially sensitive to nicotine and non-nicotine factors a continuous working memory task (CWM) and a cue-reactivity task (CR), respectively will be completed. We hypothesize that abstinence from nicotine (regardless of smoking) will result in poorer CWM performance and decreased activation of the left dorsolateral prefrontal cortex (dlPFC); while abstinence from smoking and nicotine will result in greater abstinence-induced craving and increased activation in a network of cortical, limbic and striatal regions. Individual differences in self-reported smoking motivation and other smoking-related factors will predict the effects of nicotine and non-nicotine factors on brain functioning. In addition, a sample of 36 nonsmokers will also be scanned and smoker-nonsmoker group differences will be examined. The findings of this study will shed new light on the neurobiological basis of tobacco dependence and provide a framework for understanding individual differences in tobacco use, withdrawal and relapse. Moreover, it will provide basic science information that will aid in development of new and potentially more effective treatments that address both nicotine and non-nicotine components of smoking. PUBLIC HEALTH RELEVANCE: Cigarette smoking is the leading cause of death and disability in the United States. There is a growing appreciation that factors other than nicotine contribute to the addictiveness of tobacco smoking. These include both sensory (taste, aroma) and behavioral (puffing, handling) factors. A better understanding of how these factors affect the brain can lead to new and more effective treatments to help smokers quit.