Causes of Naive Ethanol Avoidance in Drosophila Melanogaster

BACKGROUND: Alcohol dependence is a pressing public health concern, yet little is still known about its molecular causes. Although current studies have started to understand human addiction, Drosophila research is used as a tool to carry out more genetic and behavioral approaches that are crucial in learning about the addiction process. OBJECTIVE: The aim of this project was to understand the mechanisms of ethanol avoidance in Drosophila. METHODS: I applied quantitative ingestion assays to determine the amounts of food flies ate, with or without supplemented ethanol. I also used a choice assay, the FRAPPE, to determine whether naive flies exhibited preference for 15% ethanol. To interfere with neuronal function, I used the Gal4/UAS system, which allows for tissue specific manipulation of the activity of both neurons and genes. RESULTS: On average, Drosophila flies ate less sucrose when ethanol was added. One reason for this was that fewer flies initiated feeding. Upon silencing of gustatory neurons that perceive aversive tastes, flies showed less aversion to ethanol-containing food in the choice FRAPPE assay. As I increased the starvation time, almost all flies initiated feeding, but consumption amounts were still lowered when ethanol was supplemented. Additional feeding experiments where flies were only exposed to ethanol odor, but were unable to touch it, suggested that ethanol odor also suppresses food intake. I corroborated this with ethanol vapor exposures of defined intensity and duration: during the first minute of exposure, ethanol vapor stimulated food intake, but beyond that, it caused a suppression. Mutation in the ics gene affected ethanol-induced food suppression, but had no effect on the initial ethanol-induced stimulation of food intake. CONCLUSION: Drosophila flies show multimodal suppression of food intake by ethanol. Both the taste and smell of ethanol can reduce sucrose consumption. Interestingly, ethanol odor initially enhanced, but with continued exposure suppressed food intake. This suppression was abolished in ics mutants. This gene, whose human ortholog is linked to alcohol abuse disorders, is therefore critical for alcohol aversion, explaining how ics mutant flies show high, naive preference for ethanol-containing food.