Mechanisms of diet modulating experience-dependent amphetamine preference

ABSTRACT Substance use disorder (SUD) is a huge public health problem, with last year being a historical record of drug overdose deaths in the US, with psychostimulants being the cause of a third of those deaths. Years of addiction research indicate that both genetic and environmental factors influence SUD development. However, as of today there are no FDA-approved drugs to treat psychostimulant use disorder. Therefore, new approaches are needed. Recent studies demonstrate that diet influences mental health, including SUD behaviors: diet influences alcohol drinking and recovery from SUD among others. Despite the evidence linking diet with SUD, mechanistic insight into how diet and the gut affect SUD development is missing. My proposal aims to elucidate the molecules and mechanisms of gut-brain communication that modulate dopaminergic neurons and SUD-related behavior by taking advantage of the genetic tools, fast generation time and high-throughput economy of scale of Drosophila. To that end, I have developed a robust, quantitative assay that shows flies develop experience-dependent amphetamine preference. I propose to identify gut to brain signaling pathways as well as dietary components that alter dopaminergic signaling and amphetamine preference. This proposal leverages my previous knowledge in Drosophila behavior and will provide training in SUD-related behaviors. Carrying out the career plan outlined will enable me to achieve my long-term career goal: to become an independent investigator with a research program focused on the role of diet as a risk factor and possible treatment for SUD.