| First Author | Maiya R | Year | 2016 |
| Journal | Neuropharmacology | Volume | 107 |
| Pages | 40-48 | PubMed ID | 26947945 |
| Mgi Jnum | J:318798 | Mgi Id | MGI:6859334 |
| Doi | 10.1016/j.neuropharm.2016.02.036 | Citation | Maiya R, et al. (2016) Selective chemical genetic inhibition of protein kinase C epsilon reduces ethanol consumption in mice. Neuropharmacology 107:40-48 |
| abstractText | Reducing expression or inhibiting translocation of protein kinase C epsilon (PKCepsilon) prolongs ethanol intoxication and decreases ethanol consumption in mice. However, we do not know if this phenotype is due to reduced PKCepsilon kinase activity or to impairment of kinase-independent functions. In this study, we used a chemical-genetic strategy to determine whether a potent and highly selective inhibitor of PKCepsilon catalytic activity reduces ethanol consumption. We generated ATP analog-specific PKCepsilon (AS-PKCepsilon) knock-in mice harboring a point mutation in the ATP binding site of PKCepsilon that renders the mutant kinase highly sensitive to inhibition by 1-tert-butyl-3-naphthalen-1-ylpyrazolo[3,4-d]pyrimidin-4-amine (1-NA-PP1). Systemically administered 1-NA-PP1 readily crossed the blood brain barrier and inhibited PKCepsilon-mediated phosphorylation. 1-NA-PP1 reversibly reduced ethanol consumption by AS-PKCepsilon mice but not by wild type mice lacking the AS-PKCepsilon mutation. These results support the development of inhibitors of PKCepsilon catalytic activity as a strategy to reduce ethanol consumption, and they demonstrate that the AS- PKCepsilon mouse is a useful tool to study the role of PKCepsilon in behavior. |
