Diet Modification Alters Repeated Exposure Ethanol Tolerance Development.

Diet is a major environmental factor influencing alcohol‑related behaviors, yet its contribution to ethanol tolerance remains incompletely understood. Using a repeated‑exposure sedation assay in Drosophila melanogaster , we examined how high‑protein and high‑fat diets modulate the development of rapid and repeated tolerance. Flies on a standard diet exhibited both forms of tolerance, and dietary modification enhanced repeated tolerance acquisition. High‑fat feeding reduced survival, abolished rapid tolerance, and permitted only limited tolerance after repeated exposures. These findings demonstrate that diet differentially shapes ethanol sensitivity and tolerance, identifying high‑fat feeding as a potent disruptor of ethanol‑induced neuroadaptive responses in Drosophila .