THE DEVELOPMENT OF MORPHINE-TOLERANCE AND DEPENDENCE IS ASSOCIATED WITH TRANSLOCATION OF PROTEIN-KINASE-C

The development of tolerance to the analgesic effects of morphine as w ell as morphine dependence were greatly reduced by co-administration w ith morphine of GM1 ganglioside, a substance reported to block the tra nslocation of protein kinase C (PKC) from cytosol to membrane of neuro ns. Rats made tolerant to intrathecal administration of morphine showe d increased membrane-bound PKC in the superficial layers (laminae I an d II) of the spinal cord dorsal horn but not in deeper layers. This in crease was prevented by co-administration with morphine of GM1 ganglio side. These results indicate that the translocation and activation of PKC may be a critical step in the development of opiate tolerance and dependence. Modulation of PKC translocation and activation may prove u seful for the management of pain and opiate addiction.