PET IMAGING OF BRAIN OPIOID RECEPTORS IN ALCOHOLISM

在美国，酗酒和酗酒是一个主要的公共健康问题，但人们对人类大脑中调节乙醇强化和其他特性的神经化学途径知之甚少。众所周知，大脑的内源性阿片系统在奖励机制中发挥着重要作用，最近它已成为阿片类拮抗剂纳曲酮治疗的靶点。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理论基础很好，但我们对健康人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)是一种非侵入性的成像方法，可以用来成像和定量许多神经标志物和u阿片受体可以通过使用经过充分验证的配体C-11卡芬太尼在人脑中进行PET成像。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。使用正电子发射计算机断层扫描技术测量局部阿片受体是一种新的方法，可以为内源性阿片系统在酒精中毒中的作用提供新的见解。本研究的具体目的是：L)测量有阳性酒精家族史的非酒精性男性和女性脑部区域MU阿片受体结合；2)测量FHP和FHN酒精性男性和女性脑部MU阿片受体的区域结合，并将其与酒精滥用的行为指标相关联；3)测量酒精依赖者控制性戒酒一个月期间区域MU阿片受体结合的变化。

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.