Ventral Striatal Addiction, Inflammation, and Metabolic Syndrome Signaling

Addiction is a national epidemic. Focusing only on animal models of self-administration and signaling cascades that mediate addiction-related behavior may not provide us with complete solutions. A better understanding of maladaptations underlying addiction may be reached by considering intersystemic biology in the context of brain circuitry function. Toward this goal we have been exploring how gastrointestinal immune state affects brain reward/aversion circuitry. In collaboration with the Yale/NIDA Neuroproteomics Center we have derived signaling libraries from male and female mouse cohorts with chemically-induced bowel inflammation, from which potential targets are now being screened with circuitry and neuron type-specific analysis. We are also conducting neuron type-specific polyribosomal transcriptomics that will allow multi-omic systems level integration to better understand the relationship between GI and reward circuitry state. These studies combined with assessment of effects on addiction behavior may provide new clinically relevant insights. A new R01 grant application to pursue this question is in preparation.