title: Antagonism of morphine analgesia by intracerebroventricular naloxonazine.
abstract: 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 microgram/rat. Although tail-flick assays also revealed naloxonazine effects, far greater doses (30 micrograms/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.
mesh_terms: D000698:Analgesia; D000818:Animals; D001921:Brain / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009270:Naloxone / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects; D017450:Receptors, Opioid, mu
chemical_list: D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D009270:Naloxone; D009020:Morphine; C034643:naloxonazine