Impact of Sleep Deprivation on Alcohol Behaviors in Presynaptic Neurons of Drosophila melanogaster

Alcohol abuse is a highly prevalent and costly issue in the United States and has been correlated with populations who experience increased rates of sleep deprivation. While previous research has found a correlation between sleep deprivation and higher rates of alcohol toxicity and sensitivity in Drosophila (De Nobrega et al., 2022), the cellular mechanisms of this are still being investigated. Currently, minimal literature exists studying the presynaptic effects of alcohol exposure in Drosophila and the effects of sleep deprivation on these mechanisms. Due to a high degree of genetic conservation between fruit flies and humans, Drosophila melanogaster is a valuable model organism for studying circadian rhythm disruption and neurobiology. We investigated the effect of inhibiting two presynaptic proteins, Dunc13 and RIM, on alcohol sensitivity and mortality following sleep deprivation in male Drosophila melanogaster. Sleep deprivation was found to increase alcohol sensitivity in flies with normal Dunc13 expression; flies with reduced Dunc13 protein expression, and in flies with knocked-down RIM expression. Among non-sleep deprived flies, haploinsufficient Dunc13 heterozygotes displayed lower alcohol sensitivity than flies with normal Dunc13 expression. However, reducing the activity of Dunc13 did not have an effect on alcohol sensitivity in sleep deprived flies. Neither sleep deprivation, nor inhibition of Dunc13 expression had a significant effect on mortality in this study.