The nociceptin/orphanin FQ receptor antagonist, [Nphe1]NC(1-13)NH2, potentiates morphine analgesia

Neuroreport. 2000 Aug 3;11(11):2369-72. doi: 10.1097/00001756-200008030-00007.


Nociceptin/orphanin FQ (NC) and its receptor (OP4) represent a novel peptide/receptor system which has been implicated in the regulation of various central functions, including pain. The aim of the present study was to explore the involvement of the endogenous NC/OP4 system in the modulation of opioid analgesia using the selective OP4 receptor antagonist [Nphe1]NC(1-13)NH2. Experiments were performed in mice exposed to acute as well as chronic treatment with morphine. [Nphe1]NC(1-13)NH2, injected i.c.v. at 30 nmol, strongly potentiated the analgesic effect of supraspinal morphine (1 nmol, i.c.v.) while it only slightly increased the antinociceptive activity of morphine given systemically (5 mg/kg, s.c.). [Nphe1]NC(1-13)NH, (30 nmol, i.c.v.) also potentiated morphine analgesia in mice made tolerant to the opiate (30 mg/kg/day for 4 days). These findings implicate the endogenous NC signaling as a modulator of morphine analgesia and tolerance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesia*
  • Animals
  • Central Nervous System / drug effects
  • Central Nervous System / metabolism
  • Dose-Response Relationship, Drug
  • Drug Interactions / physiology*
  • Drug Tolerance / physiology
  • Male
  • Mice
  • Morphine / pharmacology*
  • Narcotic Antagonists*
  • Opioid Peptides / drug effects
  • Opioid Peptides / metabolism*
  • Opioid Peptides / pharmacology*
  • Pain / drug therapy
  • Pain / physiopathology
  • Pain Measurement / drug effects
  • Peptide Fragments / pharmacology*
  • Reaction Time / drug effects
  • Receptors, Opioid / metabolism*


  • Narcotic Antagonists
  • Opioid Peptides
  • Peptide Fragments
  • Receptors, Opioid
  • nociceptin-(1-13)-NH2, NPhe(1)-
  • Morphine
  • nociceptin
  • nociceptin receptor