However, like all methods, there are some inherent weaknesses, or at least limitations to the method's application. There is limited to no predictive validity for drugs with clinical efficacy at treating alcoholism (Egli 2005). This is principally because many compounds are “false-positives” in the two-bottle test, reducing preference drinking but subsequently proving to have limited to no efficacy in tests with human alcohol-abusing populations. Even after all these years, we still do not know precisely what the motivation for drinking is. Why do some animals prefer and others avoid? Although the trait is a reasonable surrogate for alcohol's reinforcing properties, this is not the same as knowing that this is why animals elect to drink. Our inability to determine motivation definitively is compounded by the strong innate tendencies regarding novel flavors, and novel situations in general. As reviewed above, the genetics of alcohol preference is clearly intertwined with genetic approach and avoidance tendencies for other tastants. However, the principal limitation of two-bottle preference drinking in our opinion is that under most circumstances, even high preferring genotypes will not drink enough
