Anti-opioid efficacy of neuropeptide FF in morphine-tolerant mice

Brain Res. 1998 Oct 19;808(2):166-73. doi: 10.1016/s0006-8993(98)00665-9.


The modulatory effects of 1DMe (d-Tyr-Leu-(NMe)Phe-Gln-Pro-Gln-Arg-Phe-NH2), an agonist of Neuropeptide FF (NPFF) receptors, on opioid antinociceptive activity have been compared in naive and tolerant mice in the tail-flick and the hot-plate tests. In naive mice, 1DMe alone had no effect on pain threshold but decreased dose-dependently (3-22 nmol) the analgesic activity of morphine in both tests. In tolerant mice, injections of 60-fold lower doses of 1DMe (0.05-0.5 nmol) reverse morphine-induced analgesia in the tail-flick test but this anti-opioid effect was no longer observed with the highest doses of 1DMe tested (3-22 nmol). In the hot-plate test, the anti-opioid action of 1DMe was not detected, whatever doses tested. Neither the NPFF-like immunoreactivity content of spinal cord and of olfactory bulbs, nor the density of NPFF receptors in olfactory bulbs, were altered. These results indicate that a chronic morphine treatment modifies the pharmacological properties of NPFF but the type of pain test is crucial in determining NPFF effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies
  • Drug Tolerance
  • Hot Temperature
  • Male
  • Mice
  • Morphine / pharmacology*
  • Morphine Dependence / drug therapy*
  • Narcotic Antagonists / analysis*
  • Narcotic Antagonists / immunology
  • Narcotics / pharmacology*
  • Neuropeptides / pharmacology
  • Nociceptors / drug effects
  • Olfactory Bulb / chemistry
  • Olfactory Bulb / physiology
  • Oligopeptides / agonists
  • Oligopeptides / analysis*
  • Oligopeptides / immunology
  • Oligopeptides / pharmacology
  • Pain / drug therapy
  • Pain / physiopathology
  • Pain Measurement
  • Receptors, Neuropeptide / analysis
  • Receptors, Neuropeptide / immunology
  • Reflex / drug effects
  • Spinal Cord / chemistry
  • Spinal Cord / physiology


  • Antibodies
  • Narcotic Antagonists
  • Narcotics
  • Neuropeptides
  • Oligopeptides
  • Receptors, Neuropeptide
  • neuropeptide FF receptor
  • tyrosyl-leucyl-N-methylphenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide
  • Morphine
  • phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide