Anti-opioid efficacy of Neuropeptide FF in morphine-tolerant mice
Résumé
The modulatory effects of 1DMe D-Tyr-Leu-NMe Phe-Gln-Pro-Gln-Arg-Phe-NH , an agonist of Neuropeptide FF NPFF 2 receptors, on opioid antinociceptive activity have been compared in naive and tolerant mice in the tail-flick and the hot-plate tests. In Ž . naive mice, 1DMe alone had no effect on pain threshold but decreased dose-dependently 3-22 nmol the analgesic activity of morphine Ž . 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 Ž . 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.