TY - JOUR T1 - Enadoline Discrimination in Squirrel Monkeys: Effects of Opioid Agonists and Antagonists JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 215 LP - 223 VL - 297 IS - 1 AU - Galen J. Carey AU - Jack Bergman Y1 - 2001/04/01 UR - http://jpet.aspetjournals.org/content/297/1/215.abstract N2 - Squirrel monkeys were trained to discriminate i.m. injections of the κ-opioid receptor agonist enadoline (0.0017 mg/kg) from saline in a two-lever drug-discrimination procedure. Enadoline produced a reliable discriminative stimulus that was reproduced by the κ-selective agonists PD 117302, U 50,488, GR 89686A, (−)-spiradoline, ICI 204448, and EMD 61753, and by the mixed-action κ/μ-agonists bremazocine and ethylketocyclazocine. The discriminative stimulus effects of enadoline were not reproduced by the μ-selective agonist morphine, the δ-selective agonist BW373U86, the mixed-action opioids nalbuphine and nalorphine, or by the less active enantiomers of enadoline and spiradoline PD 129829 and (+)-spiradoline, respectively. The selective μ-opioid antagonist β-funaltrexamine (10.0 mg/kg) did not appreciably alter the dose-effect function for enadoline in any subject. However, the nonselective and κ-selective opioid antagonists quadazocine (0.03–3.0 mg/kg) and nor-BNI (3–10 mg/kg), and the mixed-action opioid nalbuphine (0.3–30 mg/kg) served to surmountably antagonize enadoline's discriminative stimulus effects. The antagonist effects of nor-BNI were long-lasting and did not distinguish between drugs purported to act at different κ-receptor subtypes. The present results bolster the view that common discriminative stimulus effects of enadoline and other opioids are mediated by κ-agonist actions that are surmountably antagonized by nor-BNI in a long-lasting manner. The enadoline-antagonist effects of nalbuphine support the idea that it acts with low efficacy at κ-opioid receptors. The American Society for Pharmacology and Experimental Therapeutics ER -