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Chunk #58 — Introduction — 6. Using Invertebrate Models to Study the Basis of Ethanol Phenotypes

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The epigenetic landscape of alcoholism.
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The invertebrate model, Drosophila melanogaster, has been used to identify genetic networks involved in ethanol behaviors whose components have also been identified in pre-clinical animal models to regulate ethanol behaviors (Atkinson 2009). Drosophila neuropeptide F (NPF), which is the homolog of mammalian NPY, mediates sensitivity to ethanol sedation and NPY signaling in rat amygdala has been shown to regulate anxiety and alcohol tolerance (Pandey, Ugale, et al., 2008; Pandey, Zhang, et al., 2008; Sakharkar et al., 2012; Wen, Parrish, Xu, Wu, & Shen, 2005; Zhang et al., 2010). The Drosophila BK-type Ca2+-activated potassium channel is involved in rapid tolerance to ethanol and has also been shown in the invertebrate model, C. elegans and in higher vertebrates to mediate ethanol sensitivity and tolerance (Cowmeadow, Krishnan, & Atkinson, 2005; Cowmeadow et al., 2006; Davies et al., 2003; Liu, Asuncion-Chin, Liu, & Dopico, 2006; Pietrzykowski et al., 2008). Epigenetic regulation of the BK channel gene promoter is complex and exhibits a spatio-temporal pattern of histone H4 acetylation following benzyl alcohol sedation in adult Drosophila brain. Acetylation increases become manifest at four hours after