PET IMAGING OF BRAIN OPIOID RECEPTORS IN ALCOHOLISM

酗酒时大脑阿片受体的 PET 成像

• 批准号: 6509283
• 负责人: MARY E MCCAUL
• 金额: $ 49.86万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6509283
• 关键词: alcoholism /alcohol abuse; bioimaging /biomedical imaging; brain metabolism; clinical research; craving; drug withdrawal; emotions; human subject; opioid receptor; positron emission tomography; receptor binding; relapse /recurrence; statistics /biometry; substance abuse related behavior

Alcohol abuse and alcoholism is a major public health problem in the United States, but little is known of the neurochemical pathways in the human brain that mediate the reinforcing and other properties of ethanol. The brain's endogenous opioid system is known to play an important role in reward mechanisms and recently it has been targeted in treatment efforts using the opiate antagonist naltrexone. The rationale for using opioid blockade in the treatment of alcoholism is well founded in experimental animal models of human alcohol use and abuse, but we know little about the underlying differences in the endogenous opioid system between healthy individuals and alcoholics. Positron emission tomography (PET) is a non-invasive imaging method that can be used to image and quantitate a number of neuromarkers and mu opioid receptors can be imaged in the human brain by PET using the well-validated ligand C-11 carfentanil. Our long-term goal is to better understand the function of the endogenous brain opioid system in alcohol use and abuse, and determine if it is involved in increasing the risk of alcoholism. The use of PET to measure regional mu opioid receptors is an approach that could provide new insight into the role of the endogenous opioid system in alcoholism. The specific aims of this study are: l) Measure regional mu opioid receptor binding by PET in non-alcoholic men and women with a positive family history of alcoholism.; 2) Measure regional brain mu opioid receptor binding by PET in FHP and FHN alcoholic men and women and relate regional binding to behavioral measures of alcohol abuse; and 3) Measure the change in regional mu opioid receptor binding during one month controlled abstinence from ethanol in alcoholic men and women.

酒精滥用和酒精中毒是美国的一个主要公共卫生问题，但人们对人脑中介导乙醇的强化和其他特性的神经化学途径知之甚少。众所周知，大脑的内源性阿片类系统在奖赏机制中发挥着重要作用，最近它已成为使用阿片拮抗剂纳曲酮的治疗工作的目标。使用阿片类药物阻断治疗酗酒的基本原理在人类酒精使用和滥用的实验动物模型中是有充分依据的，但我们对健康个体和酗酒者之间内源性阿片类药物系统的潜在差异知之甚少。正电子发射断层扫描 (PET) 是一种非侵入性成像方法，可用于对多种神经标记物进行成像和定量，并且可以使用经过充分验证的配体 C-11 卡芬太尼通过 PET 对人脑中的 mu 阿片受体进行成像。我们的长期目标是更好地了解内源性大脑阿片类系统在酒精使用和滥用中的功能，并确定它是否与增加酗酒风险有关。使用 PET 测量局部 mu 阿片受体是一种可以为内源性阿片系统在酗酒中的作用提供新见解的方法。本研究的具体目的是： l) 通过 PET 测量有酒精中毒家族史的非酗酒男性和女性的局部 mu 阿片受体结合情况。 2) 通过 PET 测量 FHP 和 FHN 酗酒男性和女性的区域脑 mu 阿片受体结合，并将区域结合与酒精滥用的行为测量联系起来； 3) 测量酗酒男性和女性在一个月控制性戒酒期间局部 mu 阿片受体结合的变化。