We are using genetic approaches to identify other genes required for this signaling process and hope to extrapolate our findings to CNS development in higher organisms. Sensitivity to ethanol and the development of tolerance and dependence are influenced substantially by genotype in humans, mice, and rats. In addition, evidence is emerging from studies in animal and cellular model systems that indicates that the effects of ethanol on a variety of cellular functions are mediated by changes in specific proteins. We have recently initiated studies using Drosophila as a potential model system for alcoholism. We have found that flies display many of the behaviors observed in humans after both acute and chronic exposure to ethanol.
Flies display signs of hyperactivity and incoordination followed by sedation and hypnosis.
We are isolating mutants that respond abnormally to the inebriating effects of a single ethanol exposure and mutants that have altered abilities to develop tolerance. The corresponding genes will serve as tools to study the molecular and cellular mechanisms underlying ethanol-induced responses and may, in the future, serve as genetic markers for alcoholism or targets for potential therapeutic intervention.