Modeling Initial Smoking Abstinence and Relapse Risk

描述（由申请人提供）：吸烟是美国可预防死亡的主要原因，绝大多数试图戒烟的人将在戒烟后的最初两周内复发。重要的是，在最初的几周内保持禁欲与复发风险的急剧下降有关。竞争性延续申请的第一次修订的总体目标是继续一个专注于开发和应用人类实验室模型的项目，以实验分析持续戒烟的初始阶段如何降低复发风险。在这个模型中，吸烟者被随机分配到他们获得货币强化的条件下，实现不同的戒烟持续时间。参与者每天向实验室报告两周，以验证吸烟状态，完成受试者评级表，并参与行为和其他测试。在之前的资助期间使用该模型进行的一系列实验的结果表明，持续戒烟的初始阶段可能会降低复发风险，因为（1）减少尼古丁戒断和渴望，（2）减少对吸烟的积极和消极强化的期望，（3）降低吸烟的相对强化效应;（4）增加受试者对戒烟的容易程度和对戒烟能力的信心。 在这个修订后的应用程序中，我们建议扩大该模型的范围，包括评估禁欲对线索反应，抑制反应，以及相关的大脑活动，使用功能磁共振成像。实验1将是一个彻底的，参数化的评估初步戒烟的影响，这扩大电池的行为，认知和神经生物学功能。实验2和3将使用该模型来检查两种有效的戒烟药物疗法（尼古丁替代疗法和伐尼克兰）如何增强或以其他方式改变持续戒烟的初始阶段的效果。这些药物已知会增加最初的戒断率，但关于它们是如何做到这一点的，特别是它们对大脑功能的影响，还有很多东西有待了解。总的来说，拟议的研究有可能贡献重要的新的科学知识，行为，认知和神经生物学的变化，发生在初始戒烟，可能直接降低复发风险。这些知识可以提供如何更好地针对治疗干预的见解，并以这种方式帮助更多的人成功戒烟。 公共卫生相关性：吸烟是美国可预防死亡的主要原因。试图戒烟者的复发模式表明，那些能够坚持最初两周尝试戒烟的人，长期成功的机会显著提高。这个项目的重点是实验分析行为，认知和神经生物学的变化，发生在最初几周的持续禁欲和阐明他们如何可能定位一个人的长期成功。

DESCRIPTION (provided by applicant): Cigarette smoking is the leading cause of preventable death in the U.S. The vast majority of individuals who attempt to quit smoking will relapse within the initial two weeks of the cessation effort. Importantly, sustaining abstinence through those initial weeks is associated with a precipitous decrease in relapse risk. The overarching aim of this 1st revision of a competing continuation application is to continue a project focused on the development and application of a human-laboratory model for experimentally analyzing how an initial period of sustained smoking abstinence may reduce relapse risk. In this model, smokers are randomly assigned to conditions in which they earn monetary reinforcement contingent on achieving varying durations of smoking abstinence. Participants report to the laboratory daily for two weeks to verify smoking status, complete subject-rating forms, and participate in behavioral and other testing. Results from a series of experiments conducted during the prior funding period using this model suggest that an initial period of sustained abstinence may lower relapse risk by (1) decreasing nicotine withdrawal and craving, (2) decreasing expectations of positive and negative reinforcement from smoking, (3) decreasing the relative reinforcing effects of smoking and (4) increasing subjects' perceived ease of abstaining and confidence in their ability to abstain. In this revised application we propose to expand the scope of this model by including assessments of abstinence effects on cue reactivity, inhibitory responding, and associated brain activity using fMRI. Experiment 1 will be a thorough, parametric assessment of initial smoking abstinence effects on this expanded battery of behavioral, cognitive, and neurobiological functioning. Experiments 2 and 3 will use the model to examine how two efficacious pharmacotherapies for smoking cessation (nicotine replacement therapy and varenicline) enhance or otherwise alter the effects of an initial period of sustained abstinence. These medications are known to increase initial abstinence rates, but much remains to be learned about how they do so especially their effects on brain function. Overall, the proposed studies have the potential to contribute important new scientific knowledge regarding behavioral, cognitive, and neurobiological changes that occur during initial smoking abstinence that may directly reduce relapse risk. Such knowledge may provide insights into how to better target therapeutic interventions and in that manner help more people succeed in quitting smoking. PUBLIC HEALTH RELEVANCE: Cigarette smoking is the leading cause of preventable death in the U.S. Relapse patterns among those attempting to quit smoking suggest that those who are able to persevere through the initial two weeks of trying to quit have a strikingly improved chance of long-term success. This project is focused on experimentally analyzing behavioral, cognitive, and neurobiological changes that occur during those initial weeks of sustaining abstinence and elucidating how they may position a person for longer-term success.