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）：药物滥用，包括吸烟，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在成瘾动物模型中得到广泛研究，但尽管如此，以及环境背景对治疗结果的公认临床重要性，很少有实证研究在人类中研究药物环境反应性。目前提案的总体目标是通过人体实验室、神经成像和临床研究来解决这一差距。我们之前开发并验证了一种方法，通过该方法吸烟者识别并拍摄与其吸烟可靠相关（或不相关）的环境。在一系列的研究中，我们已经证明，个人吸烟环境线索（PSE）强烈地引发渴望和促进吸烟，并独特地激活涉及情境诱导的药物寻求，尼古丁依赖和戒烟的脑区域，包括海马（HPC）和右前额叶（aINS）;并且aINS中的激活与响应于观看PSE的吸烟行为正相关。在拟议的申请中，我们将寻求进一步了解对PSE反应的神经和行为相关性及其在戒烟治疗和结果中的作用。在目标1中，我们将在120名吸烟者的样本中评估伐尼克兰与尼古丁替代物与安慰剂对PSE反应性的影响。在目标2中，我们将在48名吸烟者的样本中评估24小时禁欲对PSE、标准吸烟环境和近端线索（例如点燃香烟的图片）的脑激活和功能耦合的影响。参加实验室（目标1研究）和fMRI（目标2研究）评估的吸烟者将接受10周的戒烟期。在目标3中，我们将评估PSE反应性与戒烟结果之间的相关性，包括戒烟时间（即戒烟后的第一支烟）和复吸时间（即恢复常规吸烟）。拟议的研究将通过填补公认的成瘾行为中环境的临床重要性与药物-环境相互作用的大型临床前数据库之间的关键差距来产生重大的科学影响。临床研究和实践也将受到影响，确定一线药物解决环境反应性的程度，开发环境影响的临床前模型的人类模拟物，以及进一步完善可用于分型患者和定制干预的新型生物标志物PSE反应性。