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.