Researchers in the Messing Lab use animal models to study molecular and circuit neuroadaptations to drugs of abuse that contribute to substance use disorders. We are 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 disorders. We use a variety of molecular and genetic approaches including gene targeting, transgenic expression, RNA interference, and transcriptome analysis, together with behavioral pharmacology and electrophysiology to identify molecules and circuits that drive maladaptive behaviors associated with substance misuse. Major contributions include determining that protein kinase C epsilon, protein kinase C delta, protein kinase M zeta, N-type voltage-dependent calcium channels, and the type 1 equilibrative nucleoside transporter regulate ethanol intoxication and self-administration in mice. Research on protein kinase C epsilon in particular has led to ongoing efforts to develop inhibitors of this enzyme as treatments for pain, anxiety, and alcohol use disorder.Header image: CRF expressing neurons (red) with PKC delta expressing neurons (center, green) and substance P immunoreactive fibers (right, green) in the rat central amygdala. CeL,central nucleus, lateral subdivision; CeC, central nucleus, capsular subdivision; BLA, basolateral nucleus. (Images by Matt Pomrenze).