Ethanol dependence in Drosophila larvae




Robinson, Brooks Gregory

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Addiction to alcohol is a disease of changed behavior that is uniquely human in it's complexity. Because of this, researchers have strived to develop animal models of individual endophenotypes of alcoholism in hopes that the larger picture will eventually come into focus. Recent studies in Drosophila have shown that many complex alcohol-related behaviors are conserved in this genetic model system. The series of projects presented in this dissertation outline the first account of physiological ethanol dependence in Drosophila. We first show that Drosophila larvae are able to form conditioned associations between an aversive heat stimulus and an attractive odor. We then show that an acute, low-dose ethanol exposure disrupts this learning ability. Finally, we present data that demonstrate that larvae adapt to the presence of chronic ethanol to the point that they only perform normally in the learning assay when ethanol is present in the animal. We then propose that the major mechanism for this dependence involves ethanol regulating the acetylation level and therefore expression level of a large number of genes by inhibiting histone deacetylase enzymes. These experiments set the groundwork for the analysis of a network of genes, connected through interactions with histone deacetylase enzymes, that are involved in producing ethanol dependence.




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