The Role of Anxiety-Related Brain Circuits in Tobacco Dependence and Withdrawal

焦虑相关的大脑回路在烟草依赖和戒断中的作用

• 批准号: 9178355
• 负责人: ALEXANDER JOSEPH SHACKMAN
• 金额: $ 22.8万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-15 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9178355
• 关键词: Abstinence; Acute; Address; Alcohol or Other Drugs use; Alcohols; American; Animal Model; Anterior; Anxiety; Attention; Behavior; Behavior Therapy; Biological; Biological Assay; Biological Psychiatry; Brain; Brain imaging; Car Phone; Cause of Death; Cessation of life; Chronic; Cues; Data; Development; Ecological momentary assessment; Economic Burden; Emotional; Etiology; Face; Feeling; Female; Fright; Functional Magnetic Resonance Imaging; Goals; Hour; Human; Image; Imaging Techniques; Individual Differences; Insula of Reil; Intervention; Intervention Studies; Life; Matched Group; Measures; Mediating; Modeling; Moods; Motivation; National Institute of Drug Abuse; Neurobiology; Nicotine; Nicotine Dependence; Nicotine Withdrawal; Piper; Positive Reinforcements; Psychology; Recruitment Activity; Relapse; Research; Rest; Rewards; Rodent; Role; Shock; Slide; Smoke; Smoker; Smoking; Specificity; Staging; Strategic Planning; Stress; Structure of terminal stria nuclei of preoptic region; Symptoms; System; Techniques; Testing; Therapeutic; Thinking; Time; Tobacco; Tobacco Dependence; Tobacco smoking; Tobacco use; Translations; Withdrawal; Work; addiction; alcohol craving; anxiety states; base; brain circuitry; brain research; cingulate cortex; clinically relevant; craving; dependence relapse; deprivation; disability; drug of abuse; improved; innovation; insight; member; multilevel analysis; negative affect; network models; neural circuit; novel; pre-clinical; premature; programs; response; stressor; undue influence

Nearly 50 million Americans smoke tobacco and smoking is the leading cause of premature death and disability in the US. Although the transition from tobacco use to nicotine dependence is associated with enduring changes in multiple motivational mechanisms, most neurobiological research has focused on reward- related systems. Very little attention has been devoted to understanding the brain circuits involved in withdrawal-related negative affect in humans. This is unfortunate—heightened anxiety is a hallmark of nicotine deprivation in both rodents and humans and there is compelling evidence that this evolutionarily-conserved feature of withdrawal powerfully motivates nicotine dependence and relapse. Mechanistic work in rodents and imaging work by our group suggests the hypothesis that withdrawal-potentiated anxiety reflects alterations in a neural circuit encompassing the bed nucleus of the stria terminalis (BNST), anterior insula (AI), and mid- cingulate cortex (MCC). But the relevance of this circuitry to withdrawal in humans is unexplored and remains unknown. Leveraging our team's unique multi-disciplinary expertise, the goal of this proposal is to use an innovative combination of advanced fMRI analytic techniques and mobile phone-based ecological momentary assessment (EMA) to understand, for the first time, the relevance of anxiety-related brain circuits to chronic tobacco use and acute nicotine withdrawal in abstinent smokers. fMRI will be used to assay anxiety-related activation and functional connectivity in well matched groups of 24-hour abstinent and non-abstinent tobacco smokers (n=36/group; half female). EMA will be used to assay stressor exposure, negative affect, smoking urge/craving, alcohol/substance use, and smoking for 14 days (5x/day), including the 24-hour period of withdrawal immediately prior to the fMRI session. These data would enable us to systematically understand the relevance of anxiety-related brain circuits to: (1) acute nicotine withdrawal and (2) clinically-relevant features of mood and behavior in the real world. These objectives are closely aligned with the NIDA Strategic Plan. Addressing the first objective would afford an unprecedented opportunity to examine the translational relevance of prominent neurobiological models of addiction, guide the development of bidirectional translational models of nicotine dependence, identify new biological targets at the circuit level, and inform the develop of novel cessation aids. Addressing the second objective would refine our understanding of etiology, provide new targets for behavioral therapy, and inform the development of mobile phone-based interventions. Understanding the role of anxiety-related brain circuits in withdrawal is critical for efforts aimed at reducing the tremendous suffering and economic burden caused by tobacco dependence.

近 5000 万美国人吸烟，吸烟是导致过早死亡和死亡的主要原因 尽管从吸烟到尼古丁依赖的转变与美国的残疾有关。 随着多种动机机制的持久变化，大多数神经生物学研究都集中在奖励上 相关系统很少受到关注。 不幸的是，这对人类产生了与戒断相关的负面影响——加剧的焦虑是尼古丁的一个标志。 啮齿动物和人类都遭受剥夺，并且有令人信服的证据表明这种进化保守的 戒断的特征有力地激发了啮齿动物和尼古丁依赖和复发。 我们小组的成像工作提出了这样的假设：戒断强化的焦虑改变 神经回路包括终纹床核 (BNST)、前岛叶 (AI) 和中层 但该电路与人类戒断的相关性尚未被探索并且仍然存在。 利用我们团队独特的多学科专业知识，该提案的目标是使用 先进的功能磁共振成像分析技术与基于手机的生态瞬时的创新结合 评估（EMA），首次了解焦虑相关脑回路与慢性病的相关性 戒烟者的烟草使用和急性尼古丁戒断将用于检测与焦虑相关的情况。 24 小时戒烟和非戒烟匹配组的激活和功能连接 吸烟者（n=36/组；半数女性）将使用 EMA 来分析压力源暴露、负面情绪、吸烟。 14 天（5 次/天）内有强烈的冲动/渴望、酒精/药物使用和吸烟，包括 24 小时内 在功能磁共振成像会议之前立即退出这些数据将使我们能够系统地了解 焦虑相关脑回路与以下因素的相关性：（1）急性尼古丁戒断和（2）临床相关特征 这些目标与 NIDA 战略计划密切相关。 解决第一个目标将为检查转化提供前所未有的机会 成瘾的突出神经生物学模型的相关性，指导双向的发展 尼古丁依赖的转化模型，在电路层面识别新的生物靶标，并告知 开发新型戒烟辅助工具将完善我们对病因学的理解， 为行为治疗提供新的目标，并为基于手机的干预措施的发展提供信息。 了解与焦虑相关的大脑回路在戒断中的作用对于旨在减少戒断症状的努力至关重要 烟草依赖造成巨大痛苦和经济负担。