The etiologies of alcohol abuse and alcoholism, with onsets in early adulthood or later, clearly have developmental properties. Relatively little emphasis has been placed, however, on developmental aspects of the phenotypes studied in animal models of alcohol-related processes. Both environmental and genetic factors may underlie the developmental dynamics of biological processes. The research proposed here will emphasize genetic factors in a panel of alcohol-related phenotypes in mice. These phenotypes index voluntary alcohol consumption and sensitivity to hypnotic doses of administered alcohol. Quantitative trait loci (QTLs) have been identified in our previous work and in the work of others for these phenotypic domains. Previous studies in our laboratories have shown: (1) large reductions in alcohol preference in BALB/c mice in a period of 3 months in early life; (2) evidence that continuing availability of alcohol results in a large increase in preference in animals of this strain during the same interval; (3) increasing differentiation among strains in hypnotic dose sensitivity, with BALB/c mice developing the highest sensitivity; (4) reduction in the effect of a QTL for alcohol acceptance between about 15 weeks and about 50 weeks in animals derived from the C57BL/6 and DBA/2 strains. The proposed research will seek to replicate the findings of early developmental change in BALB/c mice and will identify and characterize the changes in QTL associations accompanying these developmental processes in an F2 intercross derived from BALB/c and C57BL/6 inbred strains.
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