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Functional Neuroimaging of Opioid Effects on Affective Experience

阿片类药物对情感体验影响的功能神经影像学

基本信息

批准号：
7556543
负责人：
K. Luan Phan
金额：
$ 22.8万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-30 至 2010-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7556543
关键词：
Acute Address Affect Affective Amygdaloid structure Animals Anterior Anxiety Area Attenuated Base of the Brain Behavior Behavioral Blinking Brain Brain imaging Brain region Collaborations Crossover Design Data Discipline Distress Dose Double-Blind Method Drug Addiction Drug Prescriptions Drug abuse Electromyography Emotional Emotions Exhibits Face Feeling Fright Functional Magnetic Resonance Imaging Future Goals Human Image Imaging Techniques Individual Ingestion Insula of Reil International Knowledge Magnetic Resonance Imaging Measures Mediating Modeling Moods Mus Nucleus Accumbens Opiate Addiction Opioid Opioid Receptor Oxycodone Pain Patient Self-Report Personal Satisfaction Pharmaceutical Preparations Physiological Placebo Control Placebos Play Populations at Risk Psychotropic Drugs Public Health Randomized Range Rate Relative (related person)Research Rewards Risk Role Signal Transduction Site Stimulus System Technology Testing Thinking Time Ventral Striatum Well in self addiction affective neuroscience base biological adaptation to stress blood oxygen level dependent cingulate cortex concept density displeasure drug abuser drug of abuse emotional distress emotional experience experience healthy volunteer human study improved negative mood neural circuit neuroimaging neuromechanism neurotransmission opioid abuse pleasure positive mood prescription document prescription drug abuse prescription procedure prevent relating to nervous system response

项目摘要

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.

描述（由申请人提供）：最近美国处方阿片类药物的滥用和成瘾现象显着增加，造成了代价高昂的公共卫生后果。阿片类药物，如羟考酮，往往会产生幸福感和愉悦感（例如“兴奋”、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。来自情感神经科学的新证据表明，边缘脑区域（例如，腹侧纹状体 [VS]/伏隔核 [NAcc]、杏仁核）在动物和人类的情绪体验和动机行为的控制中发挥着关键作用。有趣的是，这些区域含有高密度的阿片受体，并被认为是增强滥用药物作用的关键部位。然而，阿片类药物对人类情感体验和情绪相关边缘功能的影响在很大程度上尚不清楚。在这项研究中，我们建议使用带有情感（和非情感/中性）内容的图片来唤起健康志愿者的积极和消极影响。正像和负像分别与 VS/NAcc 和杏仁核的活动增加相关。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激活。主观情感体验将通过情感效价的自我报告评级（范围从不高兴到快乐）来测量，边缘脑活动（在 VS / NAcc、杏仁核中）将通过使用功能磁共振成像（fMRI）的血氧水平依赖性（BOLD）信号来测量。这些测量值将在受试者在摄入安慰剂 (PBO)、10 毫克和 20 毫克羟考酮后，在受试者内、双盲、随机、安慰剂对照、剂量反应交叉设计中观看 3 个行为功能磁共振成像会话中的情绪唤起图片时实时收集。在这个项目中，我们将人类药物滥用研究和情感和情感体验的脑成像研究中积累的知识和技术联系起来，以测试有关阿片类药物对情感体验和相关中脑边缘大脑激活具有重大滥用潜力的急性影响的具体假设。拟议的研究直接解决潜在滥用药物的情感/情绪相关机制和神经机制，以了解为什么这些药物在非医疗环境中被误用和滥用。这项研究得出的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，神经影像项目建立了一个跨学科合作网络，该网络将产生研究结果来支持涉及处方药滥用者或有处方药滥用风险人群的更大规模项目。处方止痛药（例如阿片类处方药）的滥用是美国日益严重的公共卫生问题。该项目的目标是检查羟考酮（最广泛滥用的止痛药之一）对情绪和大脑的影响，以便找出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。