Cue Incubation in Substance Use Disorders: Validation and Assessment of Mechanisms

项目摘要 物质线索反应是物质使用模式的核心过程。因为它与 复发，这是干预的一个重要目标。大鼠的机制研究表明，对药物的反应性 在禁欲的第一个月，暗示会增加，通常被称为暗示潜伏期。提示孵化有 最近在对人类的几项研究中证明，香烟，酒精，甲基苯丙胺， 可卡因的使用重要的是，暗示潜伏的程度因人而异，并且与风险有关。 复发的几率。因此，暗示孵化可能代表了一个关键的过程，索引脆弱性复发 对处于戒毒初期的人来说需要进一步开展工作，评估这一重要的 与人类的线索反应的差异，并在这一脆弱时期开发新的干预目标。 Approach.在这项研究中，我们将测试线索孵化在一个样本的可卡因使用障碍住院患者在一个 住院戒毒中心孵化的主要措施将包括自我报告的措施， 渴望，基于EEG的晚期正电位（LPP;索引注意力参与）和基于血液的大脑 衍生性神经营养因子（BDNF）;一种经过充分验证的大鼠线索潜伏期测量方法， 系统接合）。我们将包括额外的措施，候选人的机制，潜在的线索孵化 基于研究领域标准（RDoC）框架，包括控制（执行功能），唤醒， 积极和消极的效价系统（例如奖励和损失处理，反应抑制和执行， 情感图像处理）。目标.这项拟议中的工作将研究人类使用可卡因的线索孵化 disorder.我们将在主观、行为、神经和生化水平上测量潜伏期， 足够数量的参与者来检查个体之间的孵化预测因素。这些研究将 提供了一个关键的桥梁之间的动物和人类研究的孵化，和新颖的，全面的，信息 关于候选过程潜在的线索孵化在人类-与推进的效用的目标， 提示潜伏假说在人类的病因学和干预工作。

PROJECT SUMMARY Substance cue-reactivity is a central process underlying patterns of substance use. Because it is associated with relapse, it is an important target for interventions. Mechanistic research in rats indicates that reactivity to drug cues increases across the first month of abstinence, often referred to as cue incubation. Cue incubation has recently been demonstrated in several studies with humans, with cigarette, alcohol, methamphetamine, and cocaine use. Importantly, the degree of cue incubation varies between individuals, and has been related to risk of relapse in rat models. Thus, cue incubation may represent a critical process indexing vulnerabilities to relapse for humans in the early stages of drug use cessation. Further work is needed to assess this important source of variance in cue-reactivity with humans, and develop novel targets for intervention during this vulnerable period. Approach. In this study we will test for cue incubation in a sample of inpatients with cocaine use disorder in a residential drug-rehabilitation center. Primary measures of incubation will include self-report measures of craving, EEG-based late positive potential (LPP; indexing attentional engagement), and blood-based brain derived neurotrophic factor (BDNF; a well-validated measure of cue incubation in rats, indexing negative valence system engagement). We will include additional measures of candidate mechanisms underlying cue incubation based on the Research Domain Criteria (RDoC) framework, including control (executive function), arousal, and positive and negative valence systems (e.g. reward and loss processing, response inhibition and execution, and affective image processing). Goal. The proposed work will examine cue incubation in humans with cocaine use disorder. We will measure incubation at subjective, behavioral, neural, and biochemical levels, and include sufficient numbers of participants to examine predictors of incubation across individuals. These studies will provide a critical bridge between animal and human studies of incubation, and novel, comprehensive, information about candidate processes underlying cue incubation in humans – with the goal of advancing the utility of the cue incubation hypothesis in etiologic and intervention work with humans.