Partial loss of tolerance liability to morphine analgesia in mice lacking the nociceptin receptor gene

Neurosci Lett. 1997 Nov 21;237(2-3):136-8. doi: 10.1016/s0304-3940(97)00832-x.


In mice lacking the nociceptin (or orphanin FQ) receptor gene, when 10 mg/kg of morphine was subcutaneously given, a potent analgesia in the tail pinch test was observed. The analgesic effect of morphine was equivalent among wild-type, heterozygous and homozygous mutant mice. When morphine was given to such mice in a dose of 10 mg/kg once per day for 5 days, wild-type and heterozygous mice showed marked tolerance or reduction in the morphine analgesia on the 5th day, while homozygous mice showed only 50% reduction in the peripheral analgesia of morphine. These findings suggest that nociceptin or its receptor plays important roles in the in vivo mechanism for the development of morphine tolerance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / pharmacology*
  • Animals
  • Area Under Curve
  • Drug Tolerance
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Morphine / pharmacology*
  • Mutation
  • Nociceptin Receptor
  • Pain Measurement / drug effects
  • Receptors, Opioid / genetics*


  • Analgesics, Opioid
  • Receptors, Opioid
  • Morphine
  • Nociceptin Receptor
  • Oprl1 protein, mouse