Incentive salience and the neuropsychological underpinnings of cue-induced smoking relapse

诱因显着性和提示诱发吸烟复吸的神经心理学基础

• 批准号: 10213678
• 负责人: Francesco Versace
• 金额: $ 36.6万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-15 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10213678
• 关键词: Affect; Affective; Animal Model; Behavior; Behavior Control; Behavioral; Brain; Centers for Disease Control and Prevention (U.S.); Cigarette; Compulsive Behavior; Cues; Data; Development; Disease; Eating; Eating Behavior; Event-Related Potentials; Food; Fostering; Funding; General Population; Goals; Grant; Hour; Human; Hyperphagia; Impulse Control Disorders; Incentives; Individual; Individual Differences; Intervention; Knowledge; Laboratories; Lead; Mission; Modeling; Motivation; National Institute of Drug Abuse; Neurobiology; Neuropsychology; Neurosciences; Nicotine; Nicotine Withdrawal; Obesity; Participant; Process; Property; Public Health; Rattus; Relapse; Research; Rewards; Risk; Smoker; Smoking; Smoking Behavior; Stimulus; Strategic Planning; Substance abuse problem; Testing; Therapeutic Intervention; Translating; Translational Research; Translations; United States; addiction; base; cognitive neuroscience; craving; deprivation; disorder later incidence prevention; drug seeking behavior; habituation; improved; incentive salience; individual response; individualized prevention; innovation; motivated behavior; neurobehavioral; neurobiological mechanism; neurophysiology; non-smoker; personalized medicine; pre-clinical; prevent; relating to nervous system; response; smoking relapse; targeted treatment; theories; trait

PROJECT SUMMARY Progress in basic neuroscience has improved our understanding of addiction neurobiology, but what has proven difficult is translating this knowledge into effective relapse prevention treatments. Identifying the neurobiological mechanisms underlying relapse will likely promote the development of better targeted therapeutic interventions to prevent it. In our previous funding cycle, we showed that smokers with larger brain responses to cigarette- related cues than pleasant stimuli are more vulnerable to relapse than smokers with the opposite brain reactivity profile. The objective of this renewal is to identify the neuropsychological mechanisms underlying these brain reactivity profiles and determine how these mechanisms affect vulnerability to cue-induced smoking relapse. Our central hypothesis is that the brain reactivity profiles that we isolated in smokers reflect individual differences in the tendency to attribute incentive salience to cues predicting rewards, a trait that increases vulnerability to cue- induced behaviors. Our hypothesis is based on the incentive sensitization theory and it is supported by preclinical findings and our own preliminary data. Animal models show that rats prone to attributing incentive salience to discrete food-related cues (called “sign-trackers”) are more vulnerable to cue-induced drug seeking behavior than rats not prone to do so (called “goal-trackers”). Our preliminary data show that the same neuropsychological trait predicts smoking relapse in smokers and cue-induced eating in the general population. We plan to test our hypothesis by pursuing two specific aims: 1) Identify the neuropsychological underpinnings of cue-induced behaviors. We will use the neurophysiological profiles derived from our newly developed cued food delivery task to classify 100 smokers and 100 nonsmokers as sign-trackers or goal-trackers, and predict cue-induced smoking and eating behaviors in the two groups. Our working hypotheses are that a) sign-trackers (both smokers and nonsmokers) will be more prone than goal-trackers to cue-induced eating and b) smokers categorized as sign-trackers in the cued food delivery task will be more prone than goal-trackers to cue-induced smoking in a laboratory model of smoking lapse behavior. 2) Determine the effects of nicotine withdrawal on cue-induced neurobehavioral responses. All participants will undergo two laboratory sessions. At session 2, smokers will be nicotine deprived for 24 hours. We hypothesize that nicotine deprivation will increase cue-induced smoking and eating behaviors in sign-trackers but not in goal-trackers. Our innovative neurobehavioral approach will advance bi-directional translation by allowing us to tie individual neurophysiological profiles to cue-induced be- haviors in humans. This project is significant because it will fundamentally advance our understanding of the mechanisms underlying impulse control disorders, the first step toward identifying new targets for personalized prevention and treatment interventions.

项目摘要 基本神经科学的进展提高了我们对成瘾神经生物学的理解，但事实证明了 困难将这些知识转化为有效的救济预防治疗。识别神经生物学 继电器基础的机制可能会促进靶向更好的治疗干预措施的发展 防止它。在我们以前的资金周期中，我们表明了对香烟大脑反应较大的吸烟者 - 相关的提示比宜人的刺激比具有相反大脑反应性的吸烟者更容易受到缓解 轮廓。这种更新的目的是确定这些大脑的神经心理学机制 反应性谱并确定这些机制如何影响提示吸烟中继的脆弱性。我们的 中心假设是我们在吸烟者中孤立的大脑反应性谱反映了个体差异 将激励显着性归因于预测奖励的提示的趋势，这种特征增加了提示的脆弱性 诱发行为。我们的假设基于激励敏感性理论，并由临床前支持 发现和我们自己的初步数据。动物模型表明，大鼠容易将激励显着性归因于 离散食品相关的提示（称为“签名者”）更容易受到提示引起的毒品寻求行为的影响 比不容易这样做的老鼠（称为“目标追踪器”）。我们的初步数据表明相同的神经心理学 特质预测吸烟者的吸烟中继和提示引起的一般人群的饮食。我们计划测试我们的 通过追求两个具体目的假设：1）确定提示引起的神经心理学基础 行为。我们将使用从新开发的提示食品传递中得出的神经生理概况 将100名吸烟者和100名非吸烟者分类为签名轨道或目标跟踪器的任务，并预测提示引起的 两组中的吸烟和饮食行为。我们的工作假设是a）签名者（两个吸烟者 和非吸烟者）比目标追踪者更容易出现提示诱发的饮食，而b）被归类为吸烟者 在提示食品交付任务中的签名轨道士比目标追踪者更容易出现，以提示在一个中引起吸烟 吸烟行为的实验室模型。 2）确定尼古丁提取对提示诱导的影响 神经行为反应。所有参与者将参加两个实验室会议。在第2节，吸烟者将 被尼古丁剥夺了24小时。我们假设尼古丁剥夺会增加提示引起的吸烟 和签名轨道上的饮食行为，而不是目标跟踪器中的饮食行为。我们创新的神经行为方法将 通过允许我们将单个神经生理学概况与提示引起的BE- 人类的群落。该项目很重要，因为它将从根本上提高我们对 冲动控制障碍的基础机制，这是迈向确定个性化目标的第一步 预防和治疗干预措施。