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

描述(申请人提供)：药物滥用，包括吸烟，与物理环境有着千丝万缕的联系。药物-环境相互作用的行为学和神经基础在成瘾动物模型中得到了广泛的研究，但尽管如此，环境环境对治疗结果的临床重要性也得到了公认，但很少有实证工作研究人类的药物环境反应性。当前提案的首要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，吸烟者通过该方法识别并拍摄可靠地与他们的吸烟相关(或不相关)的环境。在一系列研究中，我们已经证明，个人吸烟环境线索(PSES)强烈地引发渴望并促进吸烟，并独特地激活与情境诱导的药物寻找、尼古丁依赖和戒烟有关的大脑区域，包括海马体(HPC)和右前岛(ANS)；并且ANS中的激活与观看PSES时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PSES的神经和行为相关性，以及它们在戒烟治疗和结果中的作用。在目标1中，我们将在120名吸烟者样本中评估varenicline、尼古丁替代疗法和安慰剂对PSE反应性的影响。在目标2中，我们将评估24小时戒烟对48名吸烟者的PSE、标准吸烟环境和近端线索(例如点燃的香烟图片)的反应对大脑激活和功能耦合的影响。参与实验室(AIM 1研究)和功能磁共振成像(AIM 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关系，包括戒烟时间(即戒烟后第一支烟)和复发(即恢复正常吸烟)。这项拟议的研究将填补环境在成瘾行为中的临床重要性与关于药物-环境相互作用的大型临床前数据库之间的关键差距，从而产生重大的科学影响。临床研究和实践也将受到以下方面的影响：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，以及进一步完善一种可用于患者亚型和量身定制干预的新生物标记物-PSE反应性。

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.