ASSESSMENT OF ENDOGENOUS ENKEPHALINS EFFICACY IN THE HOT PLATE TEST IN MICE - COMPARATIVE-STUDY WITH MORPHINE

The in vivo spare receptor population and the relative efficacies of m orphine and the endogenous enkephalins to alleviate thermal nociceptiv e inputs were compared by using the mu irreversible antagonist beta-fu naltrexamine (beta-FNA). Twenty-four hours after i.c.v. administration of beta-FNA at increasing concentrations (0.005-2.5 mu g), parallel r ightward shifts of both morphine and RE 101 (mixed enkephalin-degradin g-enzyme inhibitor) dose-response curves, were observed, but the conce ntration of beta-FNA required to reduce the analgesic responses was ab out 10 times higher for RE 101 (0.1 mu g) than for morphine (0.01 mu g ). The preferential involvement of mu receptors in the analgesic respo nses obtained after beta-FNA pretreatment, was supported by the inabil ity of the delta-selective antagonist naltrindole to block these effec ts. In conclusion, it seems that to elicit the same antinociceptive re sponses, enkephalins could occupy a smaller proportion of mu opioid re ceptors than morphine, suggesting that the endogenous peptides have a higher efficacy.