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

项目摘要 基础神经科学的进步提高了我们对成瘾神经生物学的理解，但什么已经证明， 困难的是将这些知识转化为有效的预防复发治疗。识别神经生物学 复发的潜在机制可能会促进更有针对性的治疗干预措施的发展 在我们之前的资助周期中，我们发现大脑对香烟的反应更大的吸烟者- 与愉快刺激相关的线索比具有相反大脑反应的吸烟者更容易复发 profile.这种更新的目的是确定这些大脑的神经心理学机制 反应谱，并确定这些机制如何影响线索诱导的吸烟复吸的脆弱性。我们 中心假设是，我们在吸烟者中分离出的大脑反应谱反映了吸烟者的个体差异。 倾向于将激励显着性归因于预测奖励的线索，这一特征增加了对线索的脆弱性， 诱导行为。我们的假设是基于激励致敏理论，并得到了临床前的支持 和我们自己的初步数据。动物模型表明，大鼠倾向于将激励显著性归因于 离散的食物相关线索（称为“信号追踪器”）更容易受到线索诱导的药物寻求行为的影响 而不是倾向于这样做的老鼠（称为“目标追踪者”）。我们的初步数据显示， 特征预测吸烟者的吸烟复发和一般人群的线索诱导饮食。我们计划测试 通过追求两个特定的目标：1）识别线索诱导的神经心理学基础 行为。我们将使用来自我们新开发的线索食物输送的神经生理学概况 将100名吸烟者和100名非吸烟者分为信号追踪者和目标追踪者，并预测线索诱导的 吸烟和饮食行为。我们的工作假设是：a）信号追踪者（都是吸烟者 和不吸烟者）比目标追踪者更倾向于线索诱导进食，而B）吸烟者被归类为 在提示送餐任务中，手势追踪者比目标追踪者更容易在提示诱导下吸烟 实验室吸烟行为模型。2)确定尼古丁戒断对线索诱导的 神经行为反应所有参与者将进行两次实验室会议。在第二阶段，吸烟者将 24小时内不吸尼古丁我们假设尼古丁剥夺会增加线索诱导吸烟 和进食行为的关系，但目标追踪者没有。我们创新的神经行为方法将 通过允许我们将个体神经生理学特征与线索诱导的be联系起来， 人体内的寄生虫这个项目意义重大，因为它将从根本上促进我们对 冲动控制障碍的潜在机制，确定个性化治疗新目标的第一步 预防和治疗干预。

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.