Desensitization of mu-opioid receptors does not modify the analgesia induced by an enkephalinase inhibitor.

Acetorphan, an enkephalinase inhibitor, or morphine was injected in mice which had received saline or morphine (32 mg/kg s.c. twice a day on 8 consecutive days) chronically. In the hot-plate test, the analgesia (increase in jump latency) induced by morphine (2 mg/kg i.p.) or by the mu selective opioid agonist, [D-Ala2,N-Me-Phe4, Gly5-ol]enkephalin (DAGO) (1.5, 3 or 6 ng/mouse i.c.v.), was significant in the saline group but was strongly decreased in morphine-pretreated mice. In contrast the analgesic effect of acetorphan (5 mg/kg i.v.) or of the delta selective opioid agonist [D-Pen2,D-Pen5]enkephalin (DPDPE) (0.75, 1.5 or 3 micrograms/mouse i.c.v.) was similar in both groups. These results suggest that the enkephalins protected by acetorphan act on the delta receptor site to produce antinociception.