NALTREXONE IN-VIVO PROTECTS MU-RECEPTORS FROM INACTIVATION BY BETA-FUNALTREXAMINE, BUT NOT KAPPA-RECEPTORS FROM INACTIVATION BY NOR-BINALTORPHIMINE

The ability of the competitive opioid antagonist, naltrexone, to protect opioid receptors from inactivation by the nonequilibrium antagonists, beta-funaltrexamine (beta-FNA) and nor-binaltorphimine (nor-BNI), was examined in vivo. Male rats were injected SC with 10 mg/kg naltrexone or saline, 30 min before being injected intracisternally (IC) with water, 10 mug 6-FNA, or 1.0 or 10 mug nor-BNI. The rats were tested for analgesic responses to either U69,593 (nor-BNI groups) or morphine (beta-FNA groups), on a 50-degrees-C hot plate, 24 h later. Morphine produced dose-related increases in the latency to paw lick in rats that received water (IC) (mean ED50 = 3.2 mg/kg). Little or no analgesia occurred after 1.0-30 mg/kg of morphine in animals that had received saline (SC) and 10 mug beta-FNA (IC) 24 h earlier. Pretreatment with 10 mg/kg naltrexone attenuated the antagonist effects of beta-FNA (morphine ED50 = 10.8 mg/kg). U69,593 also produced analgesia in animals that received water (IC) (ED50 = 0.97 mg/kg). This analgesia was dose-dependently blocked by nor-BNI for up to 7 days. Naltrexone did not inhibit the actions of nor-BNI. Thus, naltrexone prevented inactivation of mu receptors by beta-FNA but not inactivation of kappa receptors by nor-BNI, suggesting that antagonist interactions with mu receptors are different from those with kappa receptors.