Antagonism of morphine analgesia by intracerebroventricular naloxonazine

Intravenous pretreatment with naloxonazine, an irreversible and selective antagonist of mu-1 sites for over 24 hr, reduces analgesia induced by morphine as well as a series of opiates and enkephalins. The present study evaluated whether intracerebroventricular (ICV) administration of naloxonazine produces similar long-term (24 hr) reductions in morphine analgesia on the tail-flick and jump tests. Naloxonazine failed to alter baseline tail-flick latencies or jump thresholds, but antagonized in a dose-dependent manner morphine analgesia for 24 hr. Naloxone had no effect at 24 hr. Morphine actions in the jump test were quite sensitive to doses of naloxonazine as low as 1 μg/rat. Although tail-flick assays also revealed naloxonazine effects, far greater doses (30 μg/rat) were needed. Naloxonazine also shifted full morphine dose-response curves to the right. Again, naloxonazine antagonized morphine in the jump test more effectively than in the tail-flick assay. These data provide support for the involvement of the mu-1 opioid binding site in the central mediation of morphine analgesia and point out the differing sensitivities of two analgesiometric assay systems to naloxonazine.