Involvement of protein kinase Cγ isoform in morphine-induced reinforcing effects

The present study was designed to investigate the role of protein kinase C (PKC) isoform in the morphine-induced reinforcing effect in mice. An intracerebroventricular injection of calphostin C, a specific PKC inhibitor, produced a dose-dependent reduction in the morphine-induced place preference. The protein level of PKC gamma was significantly upregulated in membrane preparations of the limbic forebrain obtained from the morphine-conditioned mice compared to that from the saline-conditioned mice. However, the protein levels of PKC alpha, betaI, beta II and epsilon were not affected in the same preparation. By contrast, there were no changes in the protein level of all five PKC isoforms in the lower midbrain. Furthermore, we investigated the rewarding properties of morphine in mice lacking PKC gamma gene. A significant place preference was observed following treatment with morphine in wild-type mice, whereas such an effect of morphine was not found in PKC gamma knockout mice. These findings suggest that activated PKC gamma in the limbic forebrain following the treatment with morphine may be critical for the development and/or maintenance of reinforcing effects induced by morphine in mice. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.