Effect of Naltrexone on Craving and Ethanol-Induced Brain Activity

动物和人类研究的结果表明，乙醇的奖励特性部分源于酒精、内源性阿片和多巴胺（DA）系统之间的复杂相互作用。急性给药乙醇增加阿片肽的释放，这反过来又增加中皮质边缘系统DA的释放。纳曲酮（NTX）是一种阿片受体拮抗剂，在治疗酒精中毒的临床前和临床研究中被广泛研究。大量临床研究表明，短期使用酒精依赖患者的NTX有效地防止复发和降低渴望的水平。

Findings from animal and human studies indicate that the rewarding properties of ethanol arise in part from a complex interaction between alcohol, endogenous opiods, and dopamine (DA) systems. Acute administration of ethanol increases the release of opioid peptides, which in turn, increases the release of DA in the mesocorticolimbic system. Naltrexone (NTX), an opioid receptor antagonist, has been studied widely in both preclinical and clinical research for the treatment of alcoholism. Numerous clinical studies have shown that short-term use of NTX in alcohol-dependent patients effectively prevents relapse and reduces the level of craving. This study will involve 60 alcoholic patients between the ages of 21-50 years of age who meet diagnostic criteria for alcohol dependence. Following detoxification, patients will be randomized, using a double-blind design, to receive NTX or placebo throughout the course of their hospitalization. fMRI scans involving ethanol infusions will be performed in order to investigate NTX's effect on the BOLD response associated with brain activity during the infusions. This protocol is the first study which involves administerinig IV alcohol to treatment-seeking alcohol dependent patients. Radification of the protocol by the IRB was prolonged due to extensive deliberations concerning patient safety. To date, four individuals have been enrolled in the study.