A Forward Genetic Screen to Identify Genes Involved in Amphetamine Action - Project Summary Amphetamine (Amph) and Amph-like drugs are commonly abused psychostimulants that come with a high addiction liability. Numerous studies have shown that Amph alters the function of various proteins in the brain. Among others, proteins linked to dopamine signaling are major targets of Amph. However, despite decades of active research, the full picture of how Amph generates addiction remains far from completely understood. For example, while it is well accepted that the increase of extracellular dopamine induced by Amph, as well as by all other addictive drugs, is the first step toward addiction, it is unknown how this increase in dopamine generates physiological and behavioral modifications that ultimately lead to addiction. To identify novel proteins that will help us to elucidate the mechanism of action of Amph, we have designed a forward genetic screen using mutated strains from the Million Mutations Project (MMP). The MMP is a collection of C. elegans mutants containing already mapped and identified mutations in specific genes. Thus, using the MMP strains for a genetic screen facilitates the identification of the gene required for the behavior the screen was set for. We will screen these mutants for Amph-induced behaviors and select animals that do not respond to Amph treatments or exhibit a hyper-response to Amph. Then, using the MMP database and the genetic tools offered by C. elegans, we will identify the genes responsible for the altered response to Amph.
