Caffeine Delays Ethanol-Induced Sedation in Drosophila

Simple Summary Caffeine and ethanol are among the most commonly consumed legal psychoactive substances worldwide. They are primarily administered in beverages for arguably opposite physiological effects—caffeine is consumed as a stimulant, and ethanol is consumed as a depressant/sedative. Both caffeine and ethanol influence many biochemical pathways including adenosine receptor-mediated signaling. Caffeine is an antagonist of adenosine receptors and ethanol elevates adenosine levels, which promotes sleep. It is important to study the interaction between caffeine and alcohol because both are easily accessible and are frequently consumed together, especially by young adults. Studies on humans have found that simultaneous intake of caffeinated drinks and alcohol increases the likelihood of alcohol consumption. In this study, using fruit flies Drosophila melanogaster as a model, we show that flies raised on a caffeine-supplemented diet for as little as one day or with mutation in adenosine receptor take longer to sedate when exposed to ethanol vapors. Further research in flies, which is an excellent model for behavioral studies, on the interaction between caffeine and ethanol will improve our understanding of the biochemical effect of pharmacological and psychoactive substances on behaviors associated with alcohol use disorders. Abstract Caffeine and ethanol are among the most widely available and commonly consumed psychoactive substances. Both interact with adenosine receptor-mediated signaling which regulates numerous neurological processes including sleep and waking behaviors. In mammals, caffeine is an adenosine receptor antagonist and thus acts as a stimulant. Conversely, ethanol is a sedative because it promotes GABAergic neurotransmission, inhibits glutamatergic neurotransmission, and increases the amount of adenosine in the brain. Despite seemingly overlapping interactions, not much is known about the effect of caffeine on ethanol-induced sedation in Drosophila. In this study, using Drosophila melanogaster as a model, we show that caffeine supplementation in food delays the onset of ethanol-induced sedation in males and females of different strains. The resistance to sedation reverses upon caffeine withdrawal. Heterozygous adenosine receptor mutant flies are resistant to sedation. These findings suggest that caffeine and adenosine receptors modulate the sedative effects of ethanol in Drosophila.