Researchers in the Messing Lab study molecular and circuit adaptations to drugs of abuse that contribute to substance use disorders. We also study animal models of co-morbid conditions that confer addiction risk, such as anxiety and chronic pain. The overall goal is to identify drug targets and strategies that could lead to new treatments for substance use and related disorders. We use a variety of molecular (gene targeting, transgenic expression, RNA interference) and circuit mapping (electrophysiology, chemogenetics, immunohistochemistry, in situ hybridization) techniques in rodents to study the role of specific signaling proteins and circuits in which they reside in regulating behavior. We also use systems-based computational strategies that compare gene expression signatures of disease and pharmaceuticals to repurpose approved drugs for treating substance use disorders. Major contributions include determining that protein kinase C epsilon, protein kinase C delta, protein kinase M zeta, N-type voltage-dependent calcium channels, the type 1 equilibrative nucleoside transporter, and phosphodiesterase 4 regulate alcohol intoxication and self-administration in mice. Research on protein kinase C epsilon has led to ongoing efforts to develop an inhibitor of this enzyme as a non-opioid medication for chronic pain and a treatment for alcohol use disorder.