Researchers in the Messing Lab study molecular and circuit neuroadaptations to drugs of abuse that contribute to addiction and to co-morbid disorders such as anxiety and pain. The overall goal is to identify drug targets and strategies that could lead to new treatments. We use a variety of molecular and genetic approaches including gene targeting, transgenic expression, and RNA interference, together with behavioral pharmacology and electrophysiology to identify molecules and circuits that drive addictive behavior. 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 and nicotine addiction.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).