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Transcript
31817
Drosophila melanogaster, a Model System for High-Throughput Screening of Drug-Induced
Central Nervous System Depression
Brian Tavakoli
Mentor: Mahtab Jafari
Central nervous system (CNS) research is highly dependent on in vivo behavioral research, in which a
live animal is subjected to a sequence of tests to determine the behavioral effect of a drug. Currently,
behavioral testing on model animals is a very time-consuming, costly, and subjective process
requiring a significant amount of behavioral research expertise. The approach to model the
phenotypical effects of drugs on the central nervous system in Drosophila melanogaster offers many
advantages in efficiency. Comparisons between the fly and human genomes indicate a high degree of
conservation in fundamental biological pathways. Large-scale pharmacological screens of drugs are
possible since flies have a complex nervous system and brain, yet minimal barrier to prevent access to
central nervous system tissue. In this project, we aimed to design a method to efficiently test the
effects of drugs on the central nervous system of Drosophila melanogaster. We orally administered
different dosages of modanaifil (Provigil®), a memory-improving and mood-brightening psycho
stimulant, and tested for any significant correlations in mating success. The experiment was carried
out 121 times by competing drugged vs. non-drugged males in vying for copulation with virgin
females. A dose-response analysis concluded that at low and high doses, modanafil had a statistically
significant effect on mating success. The dose-response data proves that the drug was effectively uptaken by the subjects and the CNS was perturbed. These results offer great motivation in further
developing a model system using Drosophila melanogaster for high-throughput testing and creating a
system to cost-effectively screen compounds for the CNS.