Effects of Smoking Expectancy on the Neural Response to Reward in Human Smokers

描述(申请人提供)：吸毒成瘾的特点是对非毒品的激励和奖励反应迟钝。当上瘾的人预计很快就可能吸毒时，这种衰减似乎特别明显。非人类动物研究表明，当预期给药时，非药物奖励的贬值程度存在很大的个体差异。此外，动物研究表明，成瘾行为的几个临床相关方面可以通过与预期相关的非药物奖励贬值的个体差异来预测。到目前为止，药物使用预期对非药物奖励处理的影响的个体差异，以及这种个体差异的功能相关性，还没有在人类吸毒者中进行调查。这项建议的目标是通过研究吸烟者(n=60)对非药物奖励的神经反应的药物使用预期影响的个体差异的性质和影响，来解决这一知识差距。这项拟议研究的具体目的是：1)考察一种新的受试者内吸烟预期操纵对吸烟者对非药物(即金钱)奖励的神经反应的影响；以及2)研究吸烟预期对非药物奖励神经反应的个体差异与为了获得激励而抵制吸烟的能力之间的关系。我们假设，当预期使用药物时，个体在非药物奖励贬值的程度上会有很大差异。由于非药物激励作为戒烟行为的有效增强剂的能力很可能在很大程度上取决于它们在面对使用药物的机会时保持其价值的程度，我们还假设，预期导致非药物奖励贬值的个体差异将预测为了获得金钱而戒烟的能力。这项提议是迈向长期研究计划的第一步，该计划旨在调查在维持成瘾行为中起重要作用的奖赏加工偏差。具体地说，如果我们的预测得到支持，未来的研究将扩展拟议的研究，试图找出调节与预期相关的非药物奖励贬值的变量(例如，非药物奖励的大小和延迟)，阐明将个人内部的奖励贬值降至最低的方法(例如，个性化的激励措施)，并检查与这些方法的实施相关的期望相关贬值的变化。 与公共健康相关：吸烟仍然是世界上主要的可预防的死亡和疾病原因之一。因此，更好地了解维持尼古丁成瘾的动机因素，以及最终如何更有效地治疗这种疾病，将对公众健康产生重大好处。此外，该项目的结果将适用于以异常动机加工为特征的其他几种障碍(例如，其他物质使用障碍、饮食障碍)。

DESCRIPTION (provided by applicant): Drug addiction is characterized by a blunted response to non-drug incentives and rewards. This attenuation appears to be especially pronounced when addicted individuals anticipate that drug use soon will be possible. Non-human animal studies indicate that there are large individual differences in the extent to which non-drug rewards are devalued when drug delivery is expected. Moreover, animal research suggests that several clinically-relevant aspects of addictive behavior are predicted by individual differences in the expectancy- related devaluation of non-drug rewards. To date, individual differences in the effects of drug use expectancy on the processing of non-drug rewards, and the functional correlates of such individual differences, have not been investigated in human drug users. The goal of this proposal is to address this knowledge gap by examining the nature and implications of individual differences in the effects of drug use expectancy on neural responses to non-drug rewards in human smokers (n=60). The specific aims of the proposed research are: 1) To examine the effects of a novel within-subjects smoking expectancy manipulation on neural responses to non-drug (i.e., monetary) rewards in human smokers; and 2) To examine how individual differences in the effects of smoking expectancy on neural responses to non-drug rewards relate to the ability to resist smoking in order to obtain an incentive. We hypothesize that individuals will vary significantly in the degree to which non-drug rewards are devalued when drug use is anticipated. As the ability of non-drug incentives to serve as an effective reinforcer for abstinence behavior likely depends substantially upon the extent to which they maintain their value in the face of an opportunity to use drugs, we also hypothesize that individual differences in the expectancy-induced devaluation of non-drug rewards will be predictive of the capacity to refrain from smoking in order to obtain money. This proposal serves as an initial step towards a long-term research plan aimed at investigating the reward-processing biases that play an important role in maintaining addictive behavior. Specifically, if our predictions are supported, future studies will extend the proposed research by seeking to identify variables that modulate the expectancy-related devaluation of non-drug rewards (e.g., the magnitude and delay of the non-drug reward), elucidating approaches for minimizing reward devaluation within individuals (e.g., individually tailored incentives), and examining changes in expectancy-related devaluation associated with the implementation of such approaches. PUBLIC HEALTH RELEVANCE: Cigarette smoking remains one of the leading preventable causes of death and disease in the world. Accordingly, developing a better understanding of the motivational factors that underlie the maintenance of nicotine addiction and, ultimately, how to more effectively treat the disorder will have substantial public health benefits. Moreover, results from this project will be applicable to several other disorders characterized by aberrant motivational processing (e.g., other substance use disorders, eating disorders).