The goal of our work is to identify potential drug targets for treating substance abuse and pain through the study of signal transduction and circuit mechanisms that underlie these disorders. Our laboratory uses a variety of molecular (gene targeting, transgenic expression, RNA interference) and circuit mapping (electrophysiology, optogenetics, immunohistochemistry) techniques in rodents to study the role of specific signaling proteins and the circuits in which they reside to regulate behavior. Our 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 self-administration in mice. Our research on protein kinase C epsilon has led to ongoing efforts to develop inhibitors of this enzyme as treatments for chronic pain and nicotine and alcohol addiction. Current projects include:
- Identifying PKC epsilon substrates using ATP analog-sensitive kinase technology.
- Developing novel PKC epsilon inhibitors to reduce alcohol and nicotine self-administration and pain.
- Developing positive allosteric modulators of alpha4/beta2 nicotinic receptors to reduce alcohol consumption
- Defining the role of Lim Domain Only Protein 4 (LMO4) in drug self-administration, conditioned reward, and conditioned fear.
- Identifying corticotrophin releasing factor (CRF) circuits that regulate emotion and addiction.