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 well as morphine dependence were greatly reduced by co-administration with morphine of GM1 ganglioside, a substance reported to block the translocation of protein kinase C (PKC) from cytosol to membrane of neurons. Rats made tolerant to intrathecal administration of morphine showed increased membrane-bound PKC in the superficial layers (laminae I and II) of the spinal cord dorsal horn but not in deeper layers. This increase was prevented by co-administration with morphine of GM1 ganglioside. 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 useful for the management of pain and opiate addiction.