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受体阻断剂对甲基苯丙胺（MA）滥用者冲动选择影响的神经机制。我们提出了一个随机安慰剂对照研究的影响，延长释放NTX延迟折扣和其神经基板在这一人群。最近，从俄勒冈州波特兰的成瘾治疗中心和社区招募的戒酒MA使用者将在基线和随机化后30天使用fMRI和延迟折扣任务进行评估。我们还将在基线和30天内收集每周尿液药物筛查和调查，以监测参与者的安全性，并探索NTX对MA复发和HIV风险行为的影响。在目标1中，我们确定的神经基础的冲动选择在HIV感染的MA用户。我们假设：（a）腹侧纹状体（VS）和腹外侧前额叶皮层（VLPFC）的活动与奖赏的大小成比例;（B）前扣带皮层（ACC）和背外侧前额叶皮层（DLPFC）的活动与延迟的长度成比例;（c）前扣带皮层和顶下小叶（IPL）的活动与决策的过程成比例。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，与随机分配至安慰剂组的受试者相比，随机分配至NTX组的受试者的冲动性（对即时奖励的偏好）较基线降低（假设2.1），冲动性降低幅度最大的受试者在VS和VLPFC中对奖励幅度的脑反应降低，在ACC和DLPFC中对延迟时间的反应降低。这些效应在NTX组中更为明显（假设2.2）。拟议的工作将为内源性阿片类药物阻滞对MA使用者风险决策的影响提供第一个证据。行为数据的收集还允许探索性分析，以评估风险决策和风险行为之间的关联，并为药物辅助干预提供信息。这种治疗有可能推进国家艾滋病毒/艾滋病战略减少艾滋病毒传播的目标。 公共卫生相关性： 我们提出了一个随机安慰剂对照研究延长释放纳洛酮对甲基苯丙胺用户的冲动决策的影响。皮质激活和冲动将使用功能磁共振成像和延迟折扣任务进行评估。我们将评估纳洛酮内源性阿片受体阻滞剂对冲动性指标的影响。

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. PUBLIC HEALTH RELEVANCE: We propose a randomized placebo-controlled study of the effect of extended-release naltrexone on impulsive decision making in methamphetamines users. Cortical activation and impulsivity will be assessed using fMRI and delay discounting task. We will assess the effect of endogenous opioid blockade with naltrexone on measures of impulsivity.