Functional Neuroimaging of Opioid Effects on Affective Experience

描述（由申请人提供）：最近在美国，处方阿片类药物的滥用和成瘾明显增加，造成了昂贵的公共卫生后果。阿片类药物，如羟考酮，倾向于产生幸福感和愉悦感。“高”，兴高采烈)，也可能减少负面影响（例如，缓解情绪困扰，缓解焦虑），这可能是滥用阿片类处方药的动机。情感神经科学的新证据表明，大脑边缘区域（如腹侧纹状体/伏隔核、杏仁核）在动物和人类的情绪体验和动机行为的控制中起着关键作用。有趣的是，这些区域含有高密度的阿片受体，并被认为是药物滥用强化效应的关键部位。然而，阿片类药物对人类情感体验和情感相关边缘功能的影响在很大程度上是未知的。在这项研究中，我们建议使用带有情绪（和非情绪/中性）内容的图片来唤起健康志愿者的积极和消极情绪。正面和负面图像分别与VS/NAcc和杏仁核的活动增加有关。我们的主要目的是检查羟考酮是否改变这些边缘脑区域的情感体验和情感相关的激活。主观情感体验将通过自我报告的情感效价评分（从不愉快到愉快）来测量，边缘脑活动（在VS / NAcc，杏仁核）将通过使用功能磁共振成像（fMRI）的血氧水平依赖（BOLD）信号来测量。这些测量将在受试者在摄入安慰剂（PBO）、10mg和20mg羟考酮后，通过双盲、随机、安慰剂对照、剂量-反应交叉设计，在观察3次行为-功能磁共振成像（fmri）会话中的情感唤起图片时实时收集。在本项目中，我们将从人类药物滥用研究和情绪和情感体验的脑成像研究中积累的知识和技术联系起来，以测试具有大量滥用潜力的阿片类药物对情感体验和相关中脑边缘激活的急性影响的特定假设。拟议的研究直接涉及情感/情绪相关机制和潜在滥用药物的神经机制，以了解为什么这些药物在非医疗环境中被误用和滥用。从这项研究中得出的这种概念验证结果将为未来在滥用（或有滥用风险）处方阿片类药物的个体中进行的研究提供假设。此外，神经成像项目建立了一个跨学科合作网络，将产生研究结果，以支持涉及处方药滥用者或处方药滥用风险人群的更大规模项目。滥用处方止痛药，如阿片类处方药，是美国日益严重的公共卫生问题。该项目的目标是研究羟考酮（一种被广泛滥用的止痛药）对情绪和大脑的影响，以确定这些药物被滥用的原因，这可以帮助我们预防或治疗阿片类药物成瘾。

DESCRIPTION (provided by applicant): There has recently been a marked increase in abuse and addiction of prescription opioid medications in the U.S., with costly public health consequences. Opioids, such as oxycodone, tend produce feelings of well-being and pleasure (e.g. 'high', elation), and may also reduce negative affect (e.g., relieve emotional distress, relieve anxiety), which may underlie the motives for abuse of opioid prescription drugs. Emerging evidence from affective neuroscience shows that limbic brain regions (e.g., ventral striatum [VS] / nucleus accumbens [NAcc], amygdala) play a pivotal role in the control of emotional experience and motivational behaviors in animals and humans. Interestingly, these regions contain a high density of opioid receptors, and have been posited as critical sites for the reinforcing effects of drugs of abuse. However, the effects of opioid medications on affective experience and emotion-related limbic function in humans are largely unknown. In this study, we propose to evoke positive and negative affect in healthy volunteers using pictures with emotional (and non- emotional/neutral) content. Positive and negative images are associated with increased activity in the VS/NAcc and amygdala, respectively. Our primary aim is to examine if oxycodone changes affective experience and affect-related activation in these limbic brain regions. Subjective affective experience will be measured by self- report ratings of affective valence (ranging from displeasure to pleasure), and limbic brain activity (in the VS / NAcc, amygdala) will be measured by the Blood Oxygenation-Level Dependent (BOLD) signal using functional magnetic resonance imaging (fMRI). These measures will be collected in real-time as subjects are viewing the emotionally-evocative pictures across 3 behavioral-fMRI sessions in a within-subjects, double-blind, randomized, placebo-control, dose-response crossover design following ingestion of placebo (PBO), 10mg, and 20mg of oxycodone. In this project, we bridge the accumulated knowledge and technology from human drug abuse research and brain imaging studies of emotion and affective experience, to test specific hypotheses about the acute effects of an opioid medication with substantial abuse potential on affective experience and associated mesolimbic brain activation. The proposed research directly addresses both the affective/mood-related mechanisms and the neural mechanisms of potential drugs of abuse, to understand why these drugs are misused and abused in nonmedical contexts. Such proof-of-concept findings derived from this study will generate hypotheses for future studies to be conducted in individuals who abuse (or are at risk for abusing) prescription opioid medications. Moreover, the neuroimaging project establishes a network of cross-disciplinary collaboration that will generate findings to support a larger-scale project involving prescription drug abusers or populations at risk for prescription drug abuse. Abuse of prescription pain relievers, such as opioid prescription medications, is a growing public health problem in the U.S. The goal of this project is to examine the effects of oxycodone, one of the more widely abused pain relievers, on mood and on the brain, in order to identify an explanation on why these drugs are being misused, which can help us prevent or treat opioid addiction.