Environment Cue-Reactivity: Brain, Behavior and Clinical Outcomes in Tobacco Use

环境线索反应性：烟草使用中的大脑、行为和临床结果

• 批准号: 9282738
• 负责人: Francis Joseph McClernon
• 金额: $ 49.42万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9282738
• 关键词: Abstinence; Addictive Behavior; Address; Animal Experimentation; Animal Model; Anterior; Area; Attenuated; Behavioral; Brain; Brain region; Cause of Death; Cigarette; Clinical; Clinical Research; Coupling; Cues; Data; Databases; Development; Drug abuse; Drug usage; Environment; Extinction (Psychology); Feedback; Functional Magnetic Resonance Imaging; Goals; Hippocampus (Brain); Human; Insula of Reil; Intake; Intervention; Laboratories; Link; Mediating; Memory; Methods; Modality; Modeling; Nicotine Dependence; Nicotine Withdrawal; Outcome; Patients; Pharmaceutical Preparations; Pharmacotherapy; Physical environment; Placebos; Pre-Clinical Model; Probability; Psychological reinforcement; Psychophysiology; Relapse; Research; Role; Sampling; Satiation; Series; Smoke; Smoker; Smoking; Smoking Behavior; Time; Tobacco use; Treatment outcome; Withdrawal; Work; addiction; analog; base; brain behavior; cigarette smoking; clinical practice; craving; cue reactivity; disability; experience; individualized medicine; knowledge base; neuroimaging; neuroregulation; nicotine replacement; novel; novel marker; patient subsets; pre-clinical; preference; primary outcome; public health relevance; relating to nervous system; response; smoking cessation; smoking relapse; varenicline

DESCRIPTION (provided by applicant): Drug abuse, including cigarette smoking, is inextricably linked to the physical environment. The behavioral and neural bases of drug-environment interactions have been widely studied in animal models of addiction but despite this and the recognized clinical importance of environmental context on treatment outcomes, very little empirical work has investigated drug environment reactivity in humans. The overarching goal of the current proposal is to address this gap through human laboratory, neuroimaging and clinical research. We previously developed and validated a method by which smokers identify and then photograph environments reliably associated (or not associated) with their smoking. In a series of studies we have demonstrated that personal smoking environment cues (PSEs) robustly elicit craving and promote smoking, and uniquely activate brain regions implicated in context-induced drug seeking, nicotine dependence and cessation including the hippocampus (HPC) and right anterior insula (aINS); and that activation in aINS is positively correlated with smoking behavior in response to viewing PSEs. In the proposed application, we will seek to further understand the neural and behavioral correlates of reactivity to PSEs and their role in smoking cessation treatment and outcomes. In Aim 1 we will evaluate the effects of varenicline versus nicotine replacement versus placebo on PSE reactivity in a sample of 120 smokers. In Aim 2, we will evaluate the effects 24-h abstinence on brain activation and functional coupling in response to PSE, standard smoking environments and proximal cues (e.g. picture of a lit cigarette) in a sample of 48 smokers. Smokers who have participated in laboratory (Aim 1 Study) and fMRI (Aim 2 Study) assessments will undergo a 10 week smoking cessation period. In Aim 3, we will evaluate associations between PSE reactivity and smoking cessation outcomes including time to lapse (i.e. first cigarette after quitting) and relapse (i.e. return to regular smoking). The proposed research will have significant scientific impact by fillin the critical gap between the recognized clinical importance of the environment in addictive behavior and the large preclinical database on drug-environment interactions. Clinical research and practice will also be impacted by determining the degree to which first-line medictions address environment reactivity, the development of a human analog of preclinical models of environment effects and the further refinement of a novel biomarker-PSE reactivity-that can be used to subtype patients and tailor intervention.

描述（由申请人提供）：包括吸烟在内的药物滥用与物理环境密不可分。药物环境相互作用的行为和神经基础已经在成瘾动物模型中得到了广泛的研究，但是尽管如此，环境环境对治疗结果的公认临床重要性，但很少有经验工作调查了人类药物环境的反应性。当前建议的总体目标是通过人类实验室，神经影像学和临床研究来解决这一差距。我们以前开发了一种方法，并验证了一种吸烟者识别的方法，然后拍摄与吸烟相关的（或不关联）的方法。在一系列研究中，我们证明了个人吸烟环境提示（PSES）牢固地引起渴望和促进吸烟，并独特地激活与上下文引起的药物寻求药物，尼古丁依赖性和停止有关的大脑区域，包括海马（HPC）（HPC）和右前胰岛（AINS）； AINS中的激活与响应观察PSE的吸烟行为呈正相关。在拟议的应用中，我们将寻求进一步了解与PSE的反应性的神经和行为相关性及其在戒烟治疗和结果中的作用。在AIM 1中，我们将评估Varenicline与尼古丁替代品与安慰剂对120个吸烟者样本中PSE反应性的影响。在AIM 2中，我们将在48名吸烟者样本中评估响应PSE，标准吸烟环境和近端提示（例如LIT香烟的图片）的24小时禁欲和功能耦合的影响。参加实验室（AIM 1研究）和fMRI（AIM 2研究）评估的吸烟者将接受10周的戒烟期。在AIM 3中，我们将评估PSE反应性和戒烟结果之间的关联，包括时间的时间（即退出后的第一次香烟）和复发（即返回常规吸烟）。拟议的研究将通过填补在成瘾行为中公认的临床重要性与大型临床前数据库在药物环境相互作用中公认的临床重要性之间的关键差距，从而产生重大的科学影响。临床研究和实践还将通过确定一线培训解决环境反应性的程度，环境影响的人类类似物的发展以及新型生物标志物PSE反应的进一步完善的程度，可以用来亚型患者和调整干预。