ETHANOL INTOXICATION IN DROSOPHILA - GENETIC AND PHARMACOLOGICAL EVIDENCE FOR REGULATION BY THE CAMP SIGNALING PATHWAY

Upon exposure to ethanol, Drosophila display behaviors that are simila r to ethanol intoxication in rodents and humans. Using an inebriometer to measure ethanol-induced loss of postural control, we identified ch eapdate, a mutant with enhanced sensitivity to ethanol. Genetic and mo lecular analyses revealed that cheapdate is an allele of the memory mu tant amnesiac. amnesiac has been postulated to encode a neuropeptide t hat activates the cAMP pathway. Consistent with this, we find that enh anced ethanol sensitivity of cheapdate can be reversed by treatment wi th agents that increase cAMP levels or PKA activity. Conversely, genet ic or pharmacological reduction in PKA activity results in increased s ensitivity to ethanol. Taken together, our results provide functional evidence for the involvement of the cAMP signal transduction pathway i n the behavioral response to intoxicating levels of ethanol.