change the plasticity of the networks which regulate behavior. A group of transcriptional regulators of the molecular circadian clock have been identified to function as regulators of behavioral sensitization to cocaine in Drosophila. Subsequent studies in rodents proved the universality of those genes in mediating drug responses. The genetic pathways and molecular interactions through which circadian genes regulate drug responses has remained undefined. We hypothesize that new genes which interact with circadian genes in the regulation of behavioral sensitization to psychostimulants can be identified in a genetic screen in Drosophila. This is a goal for which Drosophila is perfectly suited, because genetic screens aimed at defining new genes can be performed relatively easy, fast and cheap. Our first aim is to devise a high-throughput method for measuring behavioral sensitization in flies by modifying the existing method for measuring activity. Second, we will undertake a directed behavioral screen by pre-selecting candidates with reported molecular interaction with circadian genes. In the third aim we will use transgenic flies and other genetic tools to investigate neural mechanisms involved in behavioral sensitization. The proposed research is innovative and relevant for human health. New gene candidates isolated in this screen could easily be translated into mammalian research where they will help in further understanding of neuroplastic changes induced by psychostimulants. Given our expertise and available resources the project has great potential to advance the field.
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- Summer '07
- DNA, behavioral sensitization, Trajanje projekta