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Neuropharmacology. 2013 Apr;67:25-31. doi: 10.1016/j.neuropharm.2012.10.013. Epub 2012 Nov 6.

Mutations in Bacchus reveal a tyramine-dependent nuclear regulator for acute ethanol sensitivity in Drosophila.

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Department of Cellular Biology and Biomedical and Health Sciences Institute, University of Georgia, 500 D. W. Brooks Drive, Athens, GA 30602, USA.


Fruit flies and humans display remarkably similar behavioral responses to ethanol intoxication. Here we report that loss-of-function mutations in the CG9894 gene (now named Bacchus or Bacc) attenuate ethanol sensitivity in flies. Bacc encodes a broadly expressed nuclear protein with a motif similar to ribosomal RNA-binding domains. The ethanol-related activity of Bacc was mapped to Tdc2-GAL4 neurons. Genetic and pharmacological analyses suggest that ethanol resistance of Bacc mutants is caused by increased tyramine β-hydroxylase (tβh) activity that results in excessive conversion of tyramine (TA) to octopmaine (OA). Thus, tβh and its negative regulator Bacc define a novel biogenic amine-mediated signaling pathway that regulates fly ethanol sensitivity. Importantly, elevated tbh activity has been shown to promote fighting behavior, raising the possibility that the Bacc/tbh pathway may regulate complex traits in addition to acute ethanol response.

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