Regulation of Craving Under Stress: Novel Model and Neural Mechanisms

压力下渴望的调节：新模型和神经机制

• 批准号: 9251010
• 负责人: Hedy Kober
• 金额: $ 29.98万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-15 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9251010
• 关键词: Accounting; Address; Alcohol or Other Drugs use; Animal Model; Animals; Anxiety; Brain region; Chronic stress; Cigarette; Cigarette Smoker; Cognition; Cognitive; Cognitive Therapy; Control Groups; Cues; Data; Drug usage; Exhibits; Feeling; Female; Food; Frequencies; Functional Magnetic Resonance Imaging; Gender; Goals; Health; Human; Individual; Individual Differences; Informal Social Control; Intervention; Knowledge; Lead; Maintenance; Measures; Modeling; Neurobiology; Nicotine; Nicotine Dependence; Nucleic Acid Regulatory Sequences; Participant; Patient Self-Report; Pharmaceutical Preparations; Phase; Prefrontal Cortex; Process; Recruitment Activity; Regulation; Reporting; Research; Route; Severities; Shock; Smoker; Smoking; Stimulus; Stress; Substance Use Disorder; System; Testing; Thinking; TimeLine; Ventral Striatum; acute stress; addiction; base; cigarette smoking; clinically relevant; cognitive control; craving; design; disorder later incidence prevention; drug craving; gender difference; improved; male; mortality; neuromechanism; novel; relapse prediction; relating to nervous system; smoking cessation; smoking relapse; trait

 DESCRIPTION (provided by applicant): Craving and the ability to regulate it are increasingly recognized for having key roles in the maintenance of addictions including nicotine dependence, and the prevention of relapse. To investigate these important processes, we developed the Regulation of Craving (ROC) task1-5. In this task, nicotine- dependent smokers are exposed to smoking-related stimuli. In the craving condition, they are instructed to think of the pleasant feelings associated with smoking, which results in cigarette craving. Then, in the regulation condition, they are instructed to use a cognitive strategy to regulate their craving for cigarettes (e.g., `think of the negative consequences associated with smoking')1. We used the ROC task and functional magnetic resonance imaging (fMRI) to demonstrate that self-reported craving is significantly reduced during the regulation condition, and that this depends on recruitment of regions in prefrontal cortex associated with cognitive control, such as dorsolateral prefrontal cortex2, 6. We have also shown that recruitment of these brain regions, in turn, modulates activity in subcortical regions that underlie craving, such as the ventral striatum2, 3, 7. Stress s another key factor contributing to drug use in general and smoking in particular8. A leading hypothesis is that stress contributes to smoking and relapse by potentiating craving and neural activity in brain regions associated with craving (including ventral striatum)9-11. However, recent research suggests that stress can also impair prefrontal function12. Thus, it is possible that stress may lead to drug use via two distinct routes: by (1) potentiating craving and neural activity in craving-related regions (as shown with other addictions), and also (2) compromising the regulation of craving via decrements to prefrontal function. To test our novel model and evaluate these alternative hypotheses we will administer the ROC task to 84 nicotine-dependent smokers, and 84 matched healthy controls during a 90-minute fMRI session. We will use threat of electric shock, which is known to induce acute stress on half of the trials. Then, we will compare (a) self-report and (b) neural activity between craving and regulation conditions, in a 2x2x2 factorial design: 2 ROC conditions (Craving vs. Regulation) x 2 Stress conditions (Threat of Shock vs. Safe from Shock) x 2 Stimulus types (Cigarettes vs. Appetitive Food control). To establish the clinical relevance of our findings, we will assess the contribution of each effect (Stress on Craving vs. on Regulation) to smoking severity. Finally, we will preliminarily explore gender and individual differences in stress, craving, and the regulation of craving, as evidence suggests they may moderate effects of stress and craving, with implications for smoking cessation. This project promises to advance our neurobiological understanding of stress, craving, and the regulation of craving, as well as their interaction and contribution to smoking. I turn, this would provide both a new theoretical framework to understand extant data on stress and substance use, and also adapt current treatments to specifically address the effects of stress of craving and its regulation.

 描述（由申请人提供）：人们越来越认识到渴望和调节它的能力在维持成瘾（包括尼古丁依赖）和预防复发方面发挥着关键作用。为了研究这些重要过程，我们开发了渴望调节（ROC）。 ）任务1-5。在这个任务中，尼古丁依赖的吸烟者受到与吸烟相关的刺激，在渴望条件下，他们被指示去思考与吸烟相关的愉快感觉，从而导致对香烟的渴望。在调节条件下，他们被指示使用认知策略来调节他们对香烟的渴望 （例如，“想想与吸烟相关的负面后果”）1我们使用 ROC 任务和功能磁共振成像 (fMRI) 来证明，自我报告的渴望在调节条件下显着减少，这取决于招募。前额叶皮层中与认知控制相关的区域，例如背外侧前额叶皮层2, 6。我们还表明，这些大脑区域的募集反过来又调节了渴望背后的皮层下区域的活动，例如腹侧皮层纹状体2, 3, 7. 压力是导致吸毒尤其是吸烟的另一个关键因素8。一个主要的假设是，压力通过增强渴望和与渴望相关的大脑区域（包括腹侧纹状体）的神经活动而导致吸烟和复吸。 9-11. 然而，最近的研究表明，压力也会损害前额功能12，因此，压力可能通过两种不同的途径导致药物使用：(1) 增强渴望和神经活动。与渴望相关的区域（如其他成瘾所示），以及（2）通过减少前额叶功能来损害对渴望的调节。为了测试我们的新模型并评估这些替代假设，我们将对 84 名尼古丁依赖者执行 ROC 任务。吸烟者和 84 名匹配的健康对照者在 90 分钟的功能磁共振成像会议中我们将使用电击威胁，已知这会在一半的试验中引起急性应激。然后，我们将比较 (a) 自我报告和(b) 渴望和调节条件之间的神经活动，采用 2x2x2 因子设计：2 个 ROC 条件（渴望与调节）x 2 压力条件（电击威胁与安全电击）x 2 种刺激类型（香烟与食欲食物）为了确定我们的研究结果的临床相关性，我们将评估每种影响（渴望的压力与调节的压力）对吸烟严重程度的影响。初步探索压力、渴望和渴望调节方面的性别和个体差异，因为有证据表明它们可能会减轻压力和渴望的影响，并对戒烟产生影响。该项目有望增进我们对压力、渴望和渴望调节的神经生物学理解。我反过来说，这将提供一个新的理论框架来理解现有的专门关于压力和物质使用的数据，以及解决吸烟的压力影响的适应性当前治疗方法。其监管。