The other general behavioral domain for which there are QTL data in rodents pertains to ethanol's reinforcing effects. The most widely used phenotype in rodents is ethanol preference drinking. Genetic differences in relative preference for ethanol-containing solutions over water have proven to be stable across a variety of laboratories and test conditions for nearly 50 years (Wahlsten et al., 2006). Many lines of rats and mice have been bred for high vs. low preference in attempts to uncover the genetic determinants (Grahame et al., 1999; Bell et al., 2006). In mouse studies with targeted gene manipulations, roughly 2/3 either increase or decrease ethanol preference drinking (Crabbe et al., 2006). There are extensive data in populations derived from B6 and D2-derived mouse lines identifying QTLs for preference drinking (see references above). Despite its ubiquitous use, a limitation of the preference phenotype is uncertainty about how directly it reflects the rewarding value of alcohol's interoceptive effects (see Leeman et al, 2010). If one genotype drinks more alcohol by choice than another, is that because it is more sensitive to ethanol's presumed positive
