Glutathione transferase modulates acute ethanol-induced sedation in Drosophila neuron.

Heavy alcohol consumption leads to neuropathological damage and alcohol use disorder (AUD), which affects the health of people and results in a cost burden. However, the genes modulating sensitivity to ethanol remains largely unknown. Here, we identified a novel gene, Drosophila glutathione transferase omega 1 (GstO1), which plays a critical role in regulating sensitivity to ethanol sedation. The GstO1 mutant flies showed highly increased ethanol sensitivity. Furthermore, the expression level of GstO1 regulates the behavioral response to ethanol, because decreasing and increasing GstO1 affects sedation sensitivity in a contrasting manner. In addition, the RNAi-mediated knockdown of GstO1 expression reveals that GstO1 mediates sensitivity to ethanol sedation in neurons, including dopaminergic and serotonergic neurons. Altogether, our findings provide the first evidence for the involvement of glutathione transferase in the response to alcohol in Drosophila and provide a novel mechanistic insight into the toxicity and sensitivity of ethanol exposure. This article is protected by copyright. All rights reserved.