The opioid receptor system and alcoholism: a genetic perspective

Over the past decade, mounting evidence has implicated the endogenous opioid receptor system as a central player in the etiology of alcohol drinking behavior in animals and alcoholism in humans. Much of this work is a product of a pharmacological approach, where differences in opioid receptor pharmacology have been found to predict drinking behavior in animal models of alcoholism, including rats and mice selectively bred for alcohol preference and avoidance. This review considers the opioid receptor system and alcoholism from a genetic standpoint, and discusses investigation into opioid receptor pharmacology in animal models of alcoholism as work that paved the way for the more recent molecular genetic studies implicating the delta-, and particularly, the mu opioid receptors as genetically linked to alcoholism-associated phenotypes in animal models of the disease. These genetic studies are set within the broader context of the candidate gene approach for alcoholism, where opioid receptor genes are taken to be partial, rather than complete, risk factors for alcoholism. Building upon these findings, the recent genetic association between alcoholism and the mu opioid receptor gene in humans is discussed. Finally, the translation of such genetic association studies between opioid receptor genes and alcoholism to a pharmacogenetic approach, allowing for the evaluation of putative relationships between genotype and pharmacological response profiles, is suggested to address the etiological question of what the molecular mechanism is underlying opioid receptor genetic risk for alcoholism phenotypes.