Dietary yeast influences ethanol sedation in Drosophila via serotonergic neuron function

Abstract

Abuse of alcohol is a major clinical problem with far‐reaching health consequences. Understanding the environmental and genetic factors that contribute to alcohol‐related behaviors is a potential gateway for developing novel therapeutic approaches for patients that abuse the drug. To this end, we have used Drosophila melanogaster as a model to investigate the effect of diet, an environmental factor, on ethanol sedation. Providing flies with diets high in yeast, a routinely used component of fly media, increased their resistance to ethanol sedation. The yeast‐induced resistance to ethanol sedation occurred in several different genetic backgrounds, was observed in males and females, was elicited by yeast from different sources, was readily reversible, and was associated with increased nutrient intake as well as decreased internal ethanol levels. Inhibition of serotonergic neuron function using multiple independent genetic manipulations blocked the effect of yeast supplementation on ethanol sedation, nutrient intake, and internal ethanol levels. Our results demonstrate that yeast is a critical dietary component that influences ethanol sedation in flies and that serotonergic signaling is required for the effect of dietary yeast on nutrient intake, ethanol uptake/elimination, and ethanol sedation. Our studies establish the fly as a model for diet‐induced changes in ethanol sedation and raise the possibility that serotonin might mediate the effect of diet on alcohol‐related behavior in other species.

Tyramine synthesis, vesicular packaging, and the SNARE complex function coordinately in astrocytes to regulate Drosophila alcohol sedation

“…To determine whether glial Tdc2 was altering alcohol sedation via a pharmacodynamic or pharmacokinetic mechanism, we measured alcohol levels in flies expressing Tdc2 RNAi via repo-Gal4 and control genotypes after prescribed periods of alcohol exposure. As expected, 31,32 internal alcohol levels significantly increased the longer flies were exposed to alcohol (Table S2, Time factor). Importantly, though, genotype did not affect internal alcohol levels (Genotype factor), indicating that constitutive pan-glial Tdc2 knockdown did not S2).…”

Receptors and Channels Associated with Alcohol Use: Contributions from Drosophila

“… 104 A recent study also found that 5-HT signaling in flies was required for dietary yeast-induced increases in alcohol consumption and resistance to sedation. 105 This study highlights the conserved link between 5-HT, diet, and alcohol-related behavior across species. It is interesting that both adrenergic and serotonergic transmission influence mammalian alcohol-associated behaviors as it was recently discovered that flies have a novel adrenergic-like receptor (DmOcta2R).…”

The Neurotransmitters Involved in Drosophila Alcohol-Induced Behaviors

“…5HT may also be involved in the relationship between diet and ethanol sedation. In general, a high-yeast diet increases 5HT levels in the brain (Ro et al, 2016) and increases flies' resistance to alcohol sedation (Schmitt et al, 2020). Serotonergic neurons can block the sedation resistance caused by a high-yeast diet (Schmitt et al, 2020), suggesting a role for 5HT in mediating the link between diet and ethanol-related behaviors.…”