PET IMAGING OF BRAIN OPIOID RECEPTORS IN ALCOHOLISM

酗酒时大脑阿片受体的 PET 成像

• 批准号: 6371484
• 负责人: James JAMES FROST
• 金额: $ 48.75万
• 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 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6371484
• 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，但人们对人类大脑中介导乙醇强化和其他特性的神经化学途径知之甚少。已知大脑的内源性阿片系统在奖赏机制中发挥重要作用，最近它已被靶向使用阿片拮抗剂纳洛酮的治疗努力。在人类酒精使用和滥用的实验动物模型中，使用阿片类药物阻断治疗酒精中毒的基本原理是有充分依据的，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，可用于成像和定量的神经标志物和μ阿片受体的数量可以在人脑中通过PET成像，使用充分验证的配体C-11卡芬太尼。我们的长期目标是更好地了解内源性大脑阿片系统在酒精使用和滥用中的功能，并确定它是否参与增加酒精中毒的风险。使用PET来测量区域μ阿片受体是一种可以为内源性阿片系统在酒精中毒中的作用提供新见解的方法。本研究的具体目的是：1）通过PET测量具有阳性酒精中毒家族史的非酒精男性和女性的局部μ阿片受体结合。2)通过PET测量FHP和FHN酗酒男性和女性的局部脑μ阿片受体结合，并将局部结合与酗酒的行为测量相关联;和3）测量酗酒男性和女性在一个月的控制性戒酒期间局部μ阿片受体结合的变化。