Clinical Relevance of Stress Neuroadaptation in Tobacco Dependence

压力神经适应与烟草依赖的临床相关性

基本信息

批准号：
8507199
负责人：
John J. Curtin
金额：
$ 42.84万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-01 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8507199
关键词：
Abstinence Affect Affective Animal Model Animals Attenuated Biological Markers Brain Characteristics Chemosensitization Chronic Clinical Research Clinical Treatment Coupling Cues Drug usage Elements Emotional Etiology Failure Goals Human Intervention Laboratories Laboratory Research Lead Measurement Measures Mediating Methods Neurobiology Neurosciences Neurosciences Research Nicotine Outcome Outcome Measure Pharmaceutical Preparations Placebos Prevalence Procedures Process Psychophysiology Reflex action Regulation Relapse Relative (related person)Reporting Research Risk Science Smoker Smoking Stress Structure Substance Withdrawal Syndrome System Tobacco Dependence Tobacco use Translating Treatment outcome Uncertainty Withdrawal Withdrawal Symptom Withholding Treatment addiction base biological adaptation to stress clinically relevant drug withdrawal experience neuroadaptation nicotine replacement non-smoker psychologic response smoking cessation stressor therapy development

项目摘要

DESCRIPTION (provided by applicant): Neuroscience research with animal models implicates neuroadaptation in the stress response as a critical mechanism in the etiology of addiction across multiple classes of drugs including nicotine. Repeated homeostatic adjustments in the brain's stress systems due to chronic drug administration eventually lead to persistent compensatory adaptations in the structures involved in emotional response and its regulation. Among smokers, these stress neuroadaptations result in deregulated negative affect when nicotine-deprived and provide the strong motivational press for further smoking that manifests as urge and increased risk for smoking cessation failure. Animal models have provided substantial evidence to support this stress neuroadaptation thesis in addiction However, programmatic laboratory research that examines the stress response in nicotine deprived and non- deprived smokers (relative to non-smokers) is necessary to confirm that our understanding of stress neuroadaptations from animal models translate to addiction etiology in smokers. Negative affect is the core motivational element of the human drug withdrawal syndrome across additive drugs including nicotine. Unfortunately, much of what we know about these motivationally critical affective processes in humans is based on a narrow range of measures collected in isolation. The examination of the characteristics and neurobiological substrates of negative affect has not kept pace with the rapid conceptual, methodological, and measurement advances in the affective sciences over the past decade. Moreover, complementary methods (e.g., laboratory task manipulations, clinical treatment interventions) and measurement approaches (e.g., psychophysiology, ecological momentary assessment) are rarely combined. The research in this application capitalizes on recent research with both animals and humans that has synthesized precise laboratory manipulations of stress with sensitive psycho physiological measurement of startle reflex potentiating to parse the affective response to stress into its constituent components. In particular, startle potentiating during uncertain (vs. certain) threats holds promise as a biomarker of stress neuroadaptation following chronic nicotine or other drug use. We propose to measure stress neuroadaptation in the laboratory via startle potentiating during uncertain threat in two validated cued threat tasks among nicotine deprived and non-deprived smokers and non-smokers. Smokers will be subsequently assigned to combo NRT or placebo during smoking cessation treatment and will report on episodic stressors, negative effect, smoking urge, and smoking via ecological momentary assessment procedures. Treatment outcome will be assessed at 2 weeks post-quit. The broad goals of this research are to identify etiologically relevant psycho physiological biomarkers of stress neuroadaptation that results from chronic smoking. We evaluate the impact of this stress neuroadaptation on smokers' real-world affect, urge and smoking during smoking cessation treatment. We also evaluate if NRT can attenuate the influence of this stress neuroadaptation on smoking cessation outcomes via its effects on withdrawal.

描述（由申请人提供）：使用动物模型的神经科学研究暗示，压力反应中的神经适应是在包括尼古丁在内的多种药物中成瘾的病因中的关键机制。由于长期药物给药而导致的大脑压力系统中反复的稳态调整最终导致情绪反应及其调节所涉及的结构的持续补偿性适应。在吸烟者中，这些压力神经适应导致尼古丁剥夺时会导致负面影响，并为进一步的吸烟提供了强有力的动机媒体，以表现为渴望和增加戒烟的风险。动物模型提供了大量证据，以支持成瘾中的这种压力神经适应论点，但是，有必要研究尼古丁剥夺和非剥夺吸烟者（相对于非吸烟者）的压力反应，以确认我们对吸烟者中动物模型的压力神经适应性的理解是我们对压力神经适应的理解。负面影响是包括尼古丁在内的加性药物中人类药物戒断综合征的核心动机元素。不幸的是，我们对这些动机批判性情感过程的了解大部分是基于孤立收集的狭窄措施。对负面影响的特征和神经生物学底物的检查并未与过去十年来情感科学的概念，方法论和测量的快速发展保持同步。此外，很少合并互补方法（例如，实验室任务操作，临床治疗干预措施）和测量方法（例如心理生理学，生态瞬时评估）。该应用程序中的研究利用了动物和人类的最新研究，这些研究已综合了对压力的精确实验室操纵，并通过敏感的心理生理测量对惊吓反射增强的敏感心理生理测量，从而将对压力的情感反应解析到其组成部分中。特别是，在不确定的情况下惊吓增强（与某些）威胁有望成为慢性尼古丁或其他药物使用后压力神经适应的生物标志物。我们建议通过在尼古丁被剥夺和非剥夺吸烟者和非吸烟者中的两项有效的威胁任务中，在不确定的威胁中，在不确定的威胁中，通过惊吓增强在实验室中的压力神经适应。在戒烟治疗期间，吸烟者将随后分配给NRT或安慰剂，并通过生态瞬时评估程序报告情节压力，负面影响，吸烟冲动和吸烟。治疗结果将在提示后2周评估。这项研究的广泛目标是确定由长期吸烟引起的胁迫神经适应的病因相关的心理生理生物标志物。我们评估了这种压力神经适应对吸烟者在戒烟治疗期间的现实影响，敦促和吸烟的影响。我们还评估了NRT是否可以通过其对戒断的影响来减轻这种应激神经适应对吸烟结果的影响。