NEUROPEPTIDE FF RECEPTORS CONTROL MORPHINE-INDUCED ANALGESIA IN THE PARAFASCICULAR NUCLEUS AND THE DORSAL RAPHE NUCLEUS

The ability of (1DMe)Y8Fa (D.Tyr-Leu-(NMe)Phe-Gln-Pro-Gln-Arg-Phe-NH2) , a selective neuropeptide FF analog resistant to enzymatic degradatio n, to control morphine-induced analgesia was investigated in rat after microinfusion into the dorsal raphe nucleus and the nucleus parafasci cularis of the thalamus. Infusion of (IDMe)Y8Fa (2.5 nmol) in the nucl eus raphe dorsalis did not modify the animal response in the tail-imme rsion test but significantly reversed analgesia induced by coinjected morphine (27 nmol). Similarly, (IDMe)Y8Fa (5 nmol) inhibited morphine effects in the hot-plate test after co-injection into the parafascicul ar nucleus. Furthermore, (IDMe)Y8Fa injected into the parafascicular n ucleus attenuated analgesia induced by morphine injected into the nucl eus raphe dorsalis and similarly, the neuropeptide FF analog in the nu cleus raphe dorsalis decreased the effects of 27 nmol morphine injecte d in the parafascicular nucleus. The density of neuropeptide FF recept ors did not decrease in the nucleus raphe dorsalis after lesion of ser otonergic ic neurons by 5,7-dihydroxytryptamine. However, after this l esion, (IDMe)Y8Fa injected in the nucleus raphe dorsalis was no longer able to modify analgesic effects of morphine in hot-plate and tail-im mersion tests. Similarly, the serotonin (5-HT) depletion induced by a systemic administration of para-chlorophenylalanine did not modify mor phine analgesia microinjected into the nucleus raphe dorsalis and the parafascicular nucleus but blocked the ability of (1DMe)Y8Fa to revers e morphine effects in both nuclei. These data show that neuropeptide F F exerts anti-opioid effects directly into both the nucleus raphe dors alis and the parafascicular nucleus and acts also at distance on opioi d functions. Furthermore, anti-opioid effects of neuropeptide EF requi re functional serotonergic neurons although neuropeptide FF receptors are not carried on these neurons. (C) 1997 Elsevier Science B.V.