Requirement of circadian genes for cocaine sensitization in Drosophila

The circadian clock consists of a feedback loop in which clock genes are rh ythmically expressed, giving rise to cycling Levels of RNA and proteins. Fo ur of the five circadian genes identified to date influence responsiveness to free-base cocaine in the fruit fly, Drosophila melanogaster, Sensitizati on to repeated cocaine exposures, a phenomenon also seen in humans and anim al models and associated with enhanced drug craving, is eliminated in flies mutant for period, clock, cycle, and doubletime, but not in flies lacking the gene timeless. Flies that do not sensitize owing to lack of these genes do not show the induction of tyrosine decarboxylase normally seen after co caine exposure. These findings indicate unexpected roles for these genes in regulating cocaine sensitization and indicate that they function as regula tors of tyrosine decarboxylase.