NOR-BINALTORPHIMINE - AN ULTRA-LONG ACTING KAPPA-OPIOID ANTAGONIST INPIGEONS

This study assessed the ability of naltrexone and nor-binaltorphimine (NBNI) to antagonize the rate-decreasing effects of opioid agonists. F ood-restricted pigeons were trained to peck a lit key under a fixed-ra tio (FR) 20 schedule of food reinforcement. Bremazocine, a kappa-opioi d agonist, decreased food-reinforced responding (ED(50) = 0.02 mg/kg), and naltrexone (5.6 mg/kg) reduced the potency of bremazocine six-fol d. The effect of naltrexone lasted less than 24 h. A single injection of NBNI (1 mg/kg) was given to four pigeons, and the time course of an tagonism of the rate-decreasing effects of bremazocine was measured. O ne hour after NBNI was given, it was ineffective. Eight days later, NB NI produced a five-fold reduction in the potency of bremazocine. Betwe en 12 and 20 days after NBNI, it reduced the potency of bremazocine 14 -fold. NBNI continued to antagonize bremazocine for 11 weeks. Smaller doses of NBNI (0.001-0.1 mg/kg) were ineffective. The effect of NBNI w as not due to tolerance to bremazocine, since tolerance failed to deve lop to bremazocine administered repeatedly. NBNI (1 mg/kg) did not ant agonize the response rate-decreasing effects of morphine, a mu-opioid agonist, or BW373U86, a delta-opioid agonist. NBNI was an effective an d extremely long-lasting kappa-opioid antagonist in the pigeon. The du ration of action of NBNI Is among the longest yet described in any spe cies.