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.
Gelot
A
A
Institut de Pharmacologie et de Biologie Structurale, CNRS, 205 Route de Narbonne, 31077, Toulouse, France.
Francés
B
B
Roussin
A
A
Latapie
J P
JP
Zajac
J M
JM
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