In summary, a number of experimental paradigms have afforded a more comprehensive test of the effects of this polymorphism on a host of alcohol-related phenotypes. Results suggest that this variant may be associated with greater alcohol-induced reward, which is in turn consistent with the role of the opioidergic system in the hedonic properties, or liking, of alcohol as well as natural rewards (Robinson and Berridge, 1993). Inconsistencies in the literature may be associated with factors such as sample characteristics (e.g., heavy drinkers vs. alcohol-dependent samples), which in turn may serve as a proxy for stages of alcohol-related problems. Specifically, to the extent that this polymorphism is related to the reinforcing effects of alcohol, current neurobiological theories of addiction suggest that positive reinforcement is most salient early in the transition from heavy drinking to dependence, whereas late stage alcoholism is characterized primarily by negative reinforcement processes (Koob and Kreek, 2007). Nevertheless, such models of addiction have not been sufficiently translated to human samples and the transition from positive to negative reinforcement remains poorly understood in clinical populations.
