The findings discussed in Section 6 highlight some of the heterogeneity in genotypic and phenotypic characteristics found in animal models of high alcohol consumption. As discussed by Begleiter and Porjesz (1995), alcoholism, as a complex disorder with significant heterogeneity, shares characteristics commonly found in other complex neuropsychiatric diseases/disorders. These characteristics include (1) clinical heterogeneity; (2) polygenic inheritance, such that multiple genes are involved; (3) genetic heterogeneity, such that different polymorphisms/post-translational modifications of a certain gene/gene product may yield similar symptomology; (4) reduced genetic penetrance, such that not all individuals with particular genes or specific variations in a gene develop the disorder; (5) epistatic effects, such that the disorder results from interactions with alleles at different loci; and (6) phenocopies, such that the alcoholism phenotype can be expressed despite lack of a clear genetic predisposition. We propose that the selectively bred, high alcohol-consuming rats discussed herein are excellent platforms to evaluate endophenotypes associated with AUDs and the efficacy of compounds targeting alcohol abuse and dependence. We also propose that the expanded use of multiple selectively bred, high alcohol-consuming rat lines will
