Anti-opioid efficacy of neuropeptide FF in morphine-tolerant mice.
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.
Institut de Pharmacologie et de Biologie Structurale, CNRS, 205 Route de Narbonne, 31077, Toulouse, France.
A
A
Gelot
B
B
Francés
A
A
Roussin
J P
JP
Latapie
J M
JM
Zajac
D000818:Animals; D000906:Antibodies; D004361:Drug Tolerance; D006358:Hot Temperature; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000188:drug therapy*; D009292:Narcotic Antagonists / Q000032:analysis* / Q000276:immunology; D009294:Narcotics / Q000494:pharmacology*; D009479:Neuropeptides / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects; D009830:Olfactory Bulb / Q000737:chemistry / Q000502:physiology; D009842:Oligopeptides / Q000819:agonists / Q000032:analysis* / Q000276:immunology / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D010147:Pain Measurement; D018013:Receptors, Neuropeptide / Q000032:analysis / Q000276:immunology; D012018:Reflex / Q000187:drug effects; D013116:Spinal Cord / Q000737:chemistry / Q000502:physiology
D000906:Antibodies; D009292:Narcotic Antagonists; D009294:Narcotics; D009479:Neuropeptides; D009842:Oligopeptides; D018013:Receptors, Neuropeptide; C083929:neuropeptide FF receptor; C080757:tyrosyl-leucyl-N-methylphenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide; D009020:Morphine; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide