Risky Decision-Making in Methamphetamine Users: The Role of Opioid Blockade

描述(由申请人提供)： 本研究的主要目的是探讨内源性阿片类药物阻断对甲基苯丙胺(MA)滥用者冲动选择影响的神经机制。我们提出了一项随机、安慰剂对照研究，研究缓释NTX对该人群延迟折扣及其神经底物的影响。最近从俄勒冈州波特兰的成瘾治疗中心和社区招募的戒毒MA使用者将在随机分组后的基线和30天内使用功能磁共振成像和延迟折扣任务进行评估。我们还将收集每周一次的尿药筛查和基线和30天的调查，以监测参与者的安全性，并探讨NTX对MA复发和HIV危险行为的影响。在目标1中，我们确定了HIV感染的MA使用者冲动选择的神经基础。我们假设：(A)腹侧纹状体(VS)和腹外侧额叶(VLPFC)的活动将随奖赏的大小而变化，(B)前扣带回(ACC)和背外侧前额叶(DLPFC)的活动与延迟时间有关，(C)前脑岛和顶下小叶(IPL)的活动与决策过程有关。在目标2中，我们评估了内源性阿片受体阻滞剂对冲动及其神经底物的影响。我们假设，与随机服用安慰剂(假设2.1)的受试者相比，随机服用NTX的受试者将表现出从基线开始的较低的冲动性(对即时奖励的偏好)，并且冲动性降低最大的受试者将在VS和VLPFC对奖赏幅度的大脑反应降低，以及对ACC和DLPFC延迟时间的反应降低。这些影响在NTX组将更加明显(假设2.2)。这项拟议的工作将为内源性阿片类药物阻断对吸毒者风险决策的影响提供第一个证据。收集行为数据还允许进行探索性分析，以评估危险决策和危险行为之间的关联，并为药物辅助干预提供力量估计。这种治疗有可能推进减少艾滋病毒传播的国家艾滋病毒/艾滋病战略目标。

DESCRIPTION (provided by applicant): The primary goal of this proposal is to probe the neural mechanism of the effect of endogenous opioid blockade on impulsive choice in methamphetamine (MA) abusers. We propose a randomized placebo- controlled study of the effect of extended-release NTX on delay discounting and its neural substrate in this population. Recently abstinent MA users recruited from addiction treatment centers and the community in Portland, Oregon will be assessed at baseline and 30-days following randomization using fMRI and delay discounting task. We will also collect weekly urine drug screens and surveys at baseline and 30-days to monitor participant safety and explore the effects of NTX on MA relapse and HIV risk behaviors. In Aim 1, we determine the neural basis of impulsive choice in HIV-infected MA users. We hypothesize that activity (a) in ventral striatum (VS) and ventrolateral prefrontal cortex (VLPFC) will scale with magnitude of reward, (b) in anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC) with length of delay and (c) in anterior insula and the inferior parietal lobule (IPL) with the process of making a decision. In Aim 2, we assess the effect of endogenous opioid blockade on impulsivity and its neural substrate. We hypothesize that subjects randomized to NTX will show decreased impulsivity (preference for immediate rewards) from baseline compared to those randomized to placebo (hypothesis 2.1), and that subjects with the greatest decrements in impulsivity will exhibit decreased cerebral response to reward magnitude in VS and VLPFC and decreased response to length of delay in ACC and DLPFC. These effects will be more pronounced in the NTX group (Hypothesis 2.2). The proposed work will provide the first evidence for the effect of endogenous opioid blockade on risky decision-making in MA users. Collection of behavioral data also allows for exploratory analyses to assess associations between risky decision-making and risky behaviors and inform power estimates for medication-assisted interventions. Such treatments have the potential to advance the National HIV/AIDS Strategy goal of reducing HIV transmission.