How binging creates alcohol tolerance in flies

Binge drinking has lasting effects on brain activity, but it is not clear how ethanol -- the intoxicating component of alcoholic beverages -- creates these changes. One possibility is that ethanol interacts with a family of proteins (Unc13) that help control the release of neurotransmitters across the synaptic gap between neurons. In mice, worms and flies, mutations affecting Unc13 reduce activity of the cell on the transmitting side of the synapse.

Gregg Roman and colleagues previously found that fruit flies with reduced activity of the gene Dunc13 consumed significantly more ethanol than flies without the mutation. Building on these findings, the researchers now demonstrate that ethanol interferes with the binding of diacylglycerol -- a chemical compound that facilitates neurotransmitter release -- and reduces the activity of the Unc13 protein. Flies with reduced Dunc13 activity took longer to become sedated after being exposed to intoxicating levels of ethanol. The research provides new insight into the neurobiology of alcohol tolerance.