Ulrike Heberlein Studying Drugs of Abuse in Drosophila Drug abuse is one of the most devastating social and medical problems in our society, yet little is known about the mechanisms by which these drugs regulate behavior. Our laboratory is using the fruitfly Drosophila, with its accessibility to genetic and molecular analysis, to help establish the missing links between genes and drug-induced behaviors. Flies display many of the behaviors observed in mammals after both, acute and chronic exposure to ethanol.
Flies display signs of hyperactivity, incoordination, followed by sedation and hypnosis.
In addition, flies develop tolerance to ethanol and undergo 'withdrawal-like' symptoms upon ethanol removal. We have developed assays that allow the quantification of these behaviors and have isolated mutants that respond abnormally to ethanol exposure. For example, mutations in the neuropeptide gene amnesiac are overly sensitive to the sedative effects of ethanol when measured in the inebriometer. In addition to defining drug-induced behaviors and their genetic control, we have begun to map the neuroanatomical sites of drug action and their relation to specific behaviors. For this purpose we are using targeted expression of tetanus toxin light chain, which cleaves synaptobrevin and thus eliminates synaptic transmission, in specific brain regions.