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Chunk #15 — 4. Selectively bred high alcohol-consuming rat lines and their phenotypic characteristics

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Animal models for medications development targeting alcohol abuse using selectively bred rat lines: neurobiological and pharmacological validity.
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Selective breeding is a well-established, powerful genetic tool for studying the genetics of many alcohol phenotypes of interest (Crabbe, 2008). Compared to pure association studies such as genome-wide association studies (GWAS) and recombinant inbred lines (RILs) from appropriate crosses, selective breeding from a heterogeneous outbred stock can make low frequency/rare alleles (minor allele frequency <0.05) more common and, thus, be captured within the selected high or low line. The high and low lines will exhibit extreme phenotypes that greatly exceed the range found in the foundation stock. This major advantage is completely missing in GWAS and research using RILs. Additionally, selective breeding for any phenotypes (such as alcohol preference) is hypothesis driven and genetically correlated traits of the primary selected phenotype (presumedly due to pleiotropic actions of genes: Crabbe et al., 1990) can be identified and studied. The following subsections describe the five oldest selectively bred high vs. low alcohol-consuming rat lines in the world. The text gives a brief overview of neurobehavioral and neurochemical differences found between the respective lines. The brief overview focuses primarily on observations associated with