Involvement of protein kinase C gamma 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 intrac erebroventricular injection of calphostin C, a specific PKC inhibitor, prod uced a dose-dependent reduction in the morphine-induced place preference. T he protein level of PKC gamma was significantly upregulated in membrane pre parations of the limbic forebrain obtained from the morphine-conditioned mi ce 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 sa me preparation. By contrast, there were no changes in the protein level of all five PKC isoforms in the lower midbrain. Furthermore, we investigated t he rewarding properties of morphine in mice lacking PKC gamma gene. A signi ficant place preference was observed following treatment with morphine in w ild-type mice, whereas such an effect of morphine was not found in PKC gamm a knockout mice. These findings suggest that activated PKC gamma in the limbic forebrain fol lowing 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.