Between versus Within-Subject Models of the Protective Effect of Substance-Free Reward on Alcohol, Nicotine, and Marijuana Use and Problems

摘要 酒精和物质使用障碍（AUDs和SUDs）是导致肥胖的主要原因之一。 美国可预防的死亡率和医疗费用。在两个临床前 （非人类动物）和人类成瘾模型，无物质奖励已经可靠地 被认为是成瘾预防和治疗的一种有影响力的机制。无物质 奖励通常指令人愉快的、非药物刺激和活动（例如，约会，运动 娱乐）。然而，无物质奖励增加的机制 抑制物质滥用还没有得到很好理解。它可以反映一种替代， 花时间从事愉快的活动可以防止同时使用药物，或者它可以反映出 动物文献中提到的整体环境富集现象 药物本身的成瘾性。目前的建议旨在澄清这一机制 通过两种互补的方法。一是21天（每天3次）生态 瞬时评估（EMA）协议测量参与无物质愉悦的情况 活动和酒精，烟草和大麻相关的奖励，使用和后果。的 第二个是一个多方法的实验室实验方案，将表征物质相关的 与无物质奖励相比，通过自我报告问卷和大脑对 通过脑电图（EEG）测量的奖励线索。如果一个人的亲属 神经对物质的反应与自然奖励之间的不平衡，他们可能会 存在物质滥用的特定风险。此外，大脑对特定物质的反应 奖励应与EMA期间这些活动的实际参与率相对应 期这项研究的结果有可能影响治疗的结构， SUD，告知1）无物质活动参与总体上是否具有保护作用 (e.g.,通过环境富集）或以时间动态方式是保护性的（例如，通过 用无物质的快乐活动代替物质使用），以及2）如果神经 测量可以用来预测治疗因素，如相对奖励不平衡， 快乐活动参与和物质相关奖励之间的关系，反映在日常生活中， 关于物质使用的决定。

Abstract Alcohol and substance use disorders (AUDs and SUDs) are among the leading causes of preventable mortality and healthcare costs in the United States. Across both preclinical (nonhuman animal) and human models of addiction, substance-free reward has been reliably implicated as an influential mechanism of addiction prevention and treatment. Substance-free reward refers to typically pleasurable, non-drug stimuli and activities (e.g., dating, sports, entertainment). However, the mechanism by which increases in substance-free rewards suppress substance misuse is not well understood. It could reflect a substitution, whereby the time spent engaging in a pleasurable activity prevents simultaneous drug use, or it could reflect an overall environmental enrichment, which the animal literature has connected to decreased addictive potential of the drug itself. The current proposal seeks to clarify this mechanism through two complementary approaches. One is a 21-day (3 times per day) ecological momentary assessment (EMA) protocol measuring engagement in substance-free pleasurable activities and alcohol, tobacco, and marijuana-related reward, use, and consequences. The second is a multi-method lab-experimental protocol that will characterize substance-related versus substance-free reward both through self-report questionnaires and brain responses to reward cues as measured via electroencephalogram (EEG). If an individual exhibits a relative imbalance between neural responses to substances versus natural rewards, they are likely to be at specific risk for substance misuse. Additionally, brain responses to specific substance-free rewards should map onto the actual rate of engagement of these activities during the EMA period. The results of this study have the potential to influence the structure of treatments for SUDs by informing 1) whether substance-free activity engagement is protective in the aggregate (e.g., through environmental enrichment) or is protective in a temporal dynamic fashion (e.g., by replacing substance use with a substance-free pleasurable activity instead), and 2) if neural measures can be used to predict whether treatment factors, such as relative reward imbalances between pleasurable activity engagement and substance-related reward, are reflected in day-to- day decisions regarding substance use.