Although far from conclusive, evidence implicating the endogenous opioid system in the development and maintenance of alcoholism is growing. Currently available data suggest that ethanol increases opioid neurotransmission and that this activation is part of the mechanism responsible for its reinforcing effects. Findings from preclinical research indicate that ethanol consumption and ethanol-induced dopamine (DA) release are both reduced by opioid antagonists. Individual differences in endogenous opioid activity have been linked to inherited risks for alcoholism in studies comparing ethanol-preferring and nonpreferring rats, as well as in studies using targeted gene mutation (knockout) strategies. To a large extent, findings from human studies have paralleled those from the preclinical work. Persons who differ in family history of alcoholism have been shown to also differ in basal beta-endorphin activity, beta-endorphin response to alcohol, and subjective and HPA axis hormonal response to opioid antagonists. Findings from clinical trials indicate that opioid antagonists may reduce ethanol consumption in alcoholics, particularly in persons who have resumed drinking. Nevertheless, many questions remain unanswered about the use of opioid antagonists in alcoholism treatment and about the exact role of the opioid system in ethanol preference and reward. The progression of knowledge in this field suggests that many of these questions are imminently answerable, as our ability to characterize relationships between opioid activity and human behavior continues to develop. This paper summarizes both the progress that has been made and the gaps that remain in our understanding of the interactions between the endogenous opioid system and risk for alcoholism.
Copyright 2004 Elsevier Inc.