A clear difficulty is the identification of phenotypes for study in animal models, and establishing how those phenotypes related to human phenotypes. As we have emphasized throughout this Review, it was only recently demonstrated that substance use and dependence may have important genetic differences; this is best established with respect to alcohol. Since this is a recent discovery, and based on the evidence available up to a few years ago, it would have been easy to argue that these traits were qualitatively similar and only quantitatively different. Since we barely know how to distinguish different traits that relate to use of the same substance in humans, what can we really say about what traits in animals might be analogous to human traits? Which animal traits might relate to quantity or frequency of use, which to dependence, and which to neither? We do not have a full understanding of how SUD biology in model organisms relates to biology in humans. If we were to base genetic discovery for SUDs on non-human models, the utility of this approach would depend on the
