HEBERLEIN, Ulrike; Univ. of California, San Francisco: Drosophila and molecular underpinnings to ethanol susceptibility

Alcohol abuse and alcoholism are among the most devastating social and medical problems in our society, yet little is known about the mechanisms by which ethanol regulates behavior. Our laboratory uses the fruitfly Drosophila, with its accessibility to behavioral, genetic, and molecular analysis, to help establish the missing links between genes and ethanol-induced behaviors. Flies display many of the behaviors observed in mammals after both, acute and chronic exposure to ethanol. For example, ethanol activates locomotion at low doses, but depresses it at high doses. In addition, repeated ethanol exposure leads to the development of tolerance. We have devised an automated locomotor tracking system that allows us to screen for mutants that show altered behaviors in the presence of ethanol. Different mutants affect distinct phases of the locomotor response to ethanol, highlighting the complexity of even a relatively simple behavior. The genetic, behavioral, and molecular analysis of these mutants will be presented. To define the neuroanatomical sites that regulate ethanol-induced behaviors we have used targeted expression of transgene encoding a protein kinase A inhibitor to specific brain regions. These studies have revealed that a group of neurosecretory cells plays an important role in regulating the sedating effects of ethanol.