Core 1: Alcohol Research Center Behavior Core

Summary: Genetic factors strongly influence the risk for developing alcohol use disorder (AUD) along with several related phenotypes thought to impinge on AUD. The VCU-ARC seeks to better understand the molecular underpinnings of AUD through cross-species genetic analyses in humans and model organisms. Studies in the VCU-ARC have collectively identified several genes or gene families—including Clic4, COL6A3, RYR3, MEF2, GSK3B, slo1, Swi/Sni—that play key mechanistic roles in ethanol-responsive behaviors in human populations and model organisms. The planned studies in the Behavior Core will advance the overall mission of the VCU- ARC through analyses in Drosophila (fruit fly) and mouse models that explore the role of newly identified high priority target genes in behavioral responses to alcohol. The Behavior Core will utilize the suite of genetic tools available in the fly model for accelerated screening of candidate genes for roles in acute ethanol sensitivity and rapid tolerance. The Behavior Core will also use a variety of genetic tools in the mouse model for more in- depth analysis of responses to acute and repeated ethanol including ethanol sensitivity, tolerance, consumption and seeking. The planned studies of the Behavior Core will draw on the combined analytical power of the fly and mouse models to provide valuable insights into the molecular basis of behavioral responses to acute and repeated alcohol exposure. The new knowledge generated by the Behavior Core will provide a deeper understanding of mechanisms driving behavioral responses to alcohol and thereby help lay the foundation required to develop strategies to better assess AUD risk, prevention and treatment.