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(尿毒症和肥皂症)是导致 在美国，可预防的死亡率和医疗费用。在两个临床前阶段 (非人类动物)和人类的成瘾模型，无物质的奖励一直是可靠的 作为一种有影响的成瘾预防和治疗机制。不含物质 奖励是指通常令人愉悦的、非毒品的刺激和活动(例如，约会、运动、 娱乐)。然而，增加无物质奖励的机制 抑制物质滥用还没有得到很好的理解。它可能反映了一种替换，由此 花在愉快活动上的时间可以防止同时吸毒，或者它可能反映出 全面的环境丰富，动物文献已经与之联系在一起的减少 毒品本身的成瘾潜力。目前的建议旨在澄清这一机制 通过两种相辅相成的方法。一种是21天(每天3次)的生态 测量无物质快感参与度的瞬间评估(EMA)方案 活动以及与酒精、烟草和大麻相关的奖励、使用和后果。这个 第二是一个多方法的实验室实验方案，将表征与物质相关的 通过自我报告问卷和大脑反应来比较不含物质的奖励 通过脑电(EEG)测量的奖励线索。如果一个人展示了他的亲属 神经对物质的反应与自然奖励之间的不平衡，它们很可能 有滥用物质的特定风险。此外，大脑对无特定物质的反应 奖励应与这些活动在EMA期间的实际参与率相对应 句号。这项研究的结果可能会影响治疗的结构 通过告知1)不含物质的活动总体上是否具有保护作用 (例如，通过环境浓缩)或以时间动态方式保护(例如，通过 用不含物质的愉悦活动代替物质使用)，以及2)如果神经质 衡量标准可以用来预测治疗因素，如相对报酬不平衡 在愉快的活动参与和与物质相关的奖励之间，体现在日常生活中 关于物质使用的一天决定。

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.