title: The development of morphine tolerance and dependence is associated with translocation of protein kinase C.
abstract: 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.
mesh_terms: D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000201:enzymology*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology
chemical_list: D005677:G(M1) Ganglioside; D009020:Morphine; D011493:Protein Kinase C