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

项目总结 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，但已经证明 将这些知识转化为有效的复发预防治疗是困难的。鉴定神经生物学 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 来阻止它的发生。在我们之前的资金周期中，我们表明吸烟者的大脑对香烟的反应更大- 与大脑反应相反的吸烟者相比，与愉快刺激相关的线索更容易复发 侧写。这次更新的目的是确定这些大脑背后的神经心理机制。 并确定这些机制如何影响线索诱导的吸烟复发的易感性。我们的 中心假设是，我们在吸烟者中分离出来的大脑反应谱反映了吸烟者的个体差异 倾向于将激励显著归因于线索预测奖励，这一特征增加了对线索的易感性-- 诱导性行为。我们的假设建立在激励敏感化理论的基础上，并得到临床前研究的支持 调查结果和我们自己的初步数据。动物模型显示，大鼠倾向于将激励显著归因于 与食物相关的离散线索(称为“信号追踪器”)更容易受到线索诱导的寻药行为的影响。 而不是那些不倾向于这样做的老鼠(称为“目标追踪器”)。我们的初步数据显示同样的神经心理学 特征预测吸烟者的吸烟复发和普通人群中线索诱导的进食。我们计划测试我们的 通过追求两个特定的目标进行假设：1)确定线索诱导的神经心理学基础 行为。我们将使用从我们新开发的线索送餐中获得的神经生理学特征 一项任务是将100名吸烟者和100名不吸烟者归类为手势跟踪者或目标跟踪者，并预测线索诱导 两组的吸烟和进食行为。我们的工作假设是a)信号跟踪器(两个吸烟者 和非吸烟者)将比目标追踪器更容易诱发进食，以及b)吸烟者被归类为 在暗示的食物传递任务中，手势追踪器比目标追踪器更容易在... 吸烟疏忽行为的实验室模型。2)确定尼古丁戒断对线索诱导的影响 神经行为反应。所有参与者将接受两次实验室会议。在第二节课上，吸烟者将 禁食尼古丁24小时。我们假设，尼古丁剥夺会增加线索诱导的吸烟 在手势追踪器中的进食行为，但在目标追踪器中不是。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特征与线索诱导的BE-BE联系起来，推进双向翻译 人类的行为。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，为个性化确定新目标的第一步 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.