The opioid receptor system and alcoholism: a genetic perspective

Over the past decade, mounting evidence has implicated the endogenous opioi d receptor system as a central player in the etiology of alcohol drinking b ehavior in animals and alcoholism in humans. Much of this work is a product of a pharmacological approach, where differences in opioid receptor pharma cology have been found to predict drinking behavior in animal models of alc oholism, including rats and mice selectively bred for alcohol preference an d avoidance. This review considers the opioid receptor system and alcoholis m from a genetic standpoint, and discusses investigation into opioid recept or pharmacology in animal models of alcoholism as work that paved the way f or the more recent molecular genetic studies implicating the delta-, and pa rticularly, the CL opioid receptors as genetically linked to alcoholism-ass ociated phenotypes in animal models of the disease. These genetic studies a re set within the broader context of the candidate gene approach for alcoho lism, where opioid receptor genes are taken to be partial, rather than comp lete, risk factors for alcoholism. Building upon these findings, the recent genetic association between alcoholism and the IJ. opioid receptor gene in humans is discussed. Finally, the translation of such genetic association studies between opioid receptor genes and alcoholism to a pharmacogenetic a pproach, allowing for the evaluation of putative relationships between geno type and pharmacological response profiles, is suggested to address the eti ological question of what the molecular mechanism is underlying opioid rece ptor genetic risk for alcoholism phenotypes. (C) 2000 Elsevier Science B.V. All rights reserved.