CROSS-TALK AND SIGNALLING BETWEEN ETHANOL AND ACETONE DURING RAPID EXPOSURE USING DROSOPHILA MELANOGASTER AS A MODEL ORGANISM

A number of molecular targets including ion channels have been implicated in the acquisition of tolerance to alcohol-induced sedation. Behavioral characterization of slowpoke ion channel mutants in Drosophila melanogaster during ethanol exposure revealed that tolerance is multiphasic and the slowpoke channel plays a role only during the late phase of tolerance (~24 hr. post-exposure). Similarly, cross-tolerance and cross-sensitization has been shown to be common to several drugs of abuse. While it is common to observe cross sensitization and cross-tolerance reciprocally between drugs of abuse, it is not uncommon to see that phenomenon occur in a unidirectional manner.  We are studying cross-talk between different drugs using ethanol and acetone as model drugs of abuse. Exposure of Canton S flies initially to ethanol (60%) and subsequently to acetone (6%) resulted in minimal cross-tolerance to acetone.  However, exposure of Canton S flies to 6% acetone followed by 60% ethanol induced significant cross-sensitization to ethanol. Additional analysis of hyperactivity during drug exposure suggests that initial acetone exposure, 6-24 hours prior to ethanol exposure, significantly increases the hyperactivity of flies undergoing a secondary exposure to ethanol studies.  The role of slowpoke in cross-talk was also examined and it was determined that slowpoke mutants did not perturb cross-talk between acetone and ethanol and suggests other molecular targets/mechanisms are involved in cross-talk between two different drugs of abuse. In conclusion, Drosophila is a good model for analysis of drug interactions and identification of molecular targets for abused drugs.