A New Experiment Model for Cocaine's Effects on Cells

The goal of this CEBRA proposal is to use Drosophila oogenesis to develop a new mode) experimental system to study the impact of cocaine on cells. Mammalian experimental models for studying cocaine's impact on developmental and non-neural cellular processes have been useful in describing behavioral, growth and toxicity characteristics that are associated with pre- and postnatal cocaine exposure. However, such experimental models may not be the best systems for uncovering the cellular and molecular mechanisms that underlie the drug's effects on physiology and development. The establishment of the model system proposed in this application will facilitate the design of future research for discovering what specific cellular processes are directly impacted by cocaine, or indeed by other medically important drugs of abuse. The advantages of Drosophila molecular genetics have already been exploited by others to identify genes involved in cocaine's neural response, and the discovery that cocaine-fed files exhibit distinct and reproducible ovarian defects suggests that oogenesis will be an ideal system in which to identify cellular processes that are potential targets of cocaine. This system will be valuable in learning how those processes, Including signal transduction and gene regulation, relate to cocaine's known neural actions. Since many of the molecular components of the behavioral response to cocaine have been shown to be conserved between files and humans, and since the study of Drosophila has been critical to understanding cellular mechanisms of development in general, this mode) organism should be an equally effective model for discovering how cocaine interferes with cellular functions.

The work proposed has two specific goals: to identify primary cellular processes whose disruption accounts for cocaine's deleterious effects on Drosophila oogenesis and to identify potential physiological causes for observed overlaps between cocaine behavioral sensitivity and oogenesis in Drosophila.