Engel GL1, Adhikari P1, Marella S2, Kaun KR3, Wu J2, Kong EC2, Wolf FW1,2 *
1 University of California, Merced, School of Natural Sciences, Merced, CA 95343 USA
2 Ernest Gallo Clinic and Research Center, University of California San Francisco, Emeryville, CA 94608 USA
3 Brown University, Department of Neuroscience, Providence, RI 02912 USA
Acute ethanol inebriation causes neuroadaptive changes in behavior that favor increased intake. Ethanol-induced alterations in gene expression, through epigenetic and other means, are likely to change cellular and neural circuit function. Ethanol markedly changes histone acetylation, and the sirtuin Sir2/SIRT1 that deacetylates histones and transcription factors is essential for the rewarding effects of chronic drug use. We find that Sir2 in the mushroom bodies of the fruit fly Drosophila promotes acute ethanol-induced behavioral plasticity by allowing changes in the expression of presynaptic molecules. Our findings tie the gene regulatory effects of acute ethanol to ethanol-induced behavioral plasticity in a brain region that associates context with innate approach and avoidance responses. How these ethanol-induced molecular changes impact neuronal function and also interface with other molecular and cellular effects of acute ethanol will help define how circuits change to reinforce drug intake.