We reiterate that the HDID-1 mouse is not intended to serve as a genetic model for alcoholism. Like McClearn (31), we do not believe that a plausible rodent model that fully resembles clinical alcoholism is a feasible goal (32). This is primarily because many of the diagnostic criteria for alcohol dependence are behavioral and are defined in ways that undermine the face validity of rodent models (e.g., difficulty with relationships or work). Rather, we are attempting to model one salient feature, a single binge episode. The DID model is rapid and simple, and this is its greatest strength. It is clearly different from human alcoholic drinking in several obvious ways. Whatever its pattern, alcoholic drinking is developed after years, and we would not expect the neurobiological changes seen after DID in mice to reflect the same changes achieved by a chronic alcoholic. In the current generation of HDID-1 mice, DID intakes are reduced when there is water available. However, if intakes continue to increase with further selection, we may well see significant intoxication in HDID-1 mice even when water is
