Vol. 297, Issue 1, 215-223, April 2001

Enadoline Discrimination in Squirrel Monkeys: Effects of Opioid Agonists and Antagonists

Galen J. Carey and Jack Bergman

Schering-Plough Research Institute, Kenilworth, New Jersey (G.J.C.) and Harvard Medical School, McLean Hospital ADARC, Belmont, Massachusetts (J.B.)

Squirrel monkeys were trained to discriminate i.m. injections of the -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 -selective agonists PD 117302, U 50,488, GR 89686A, ()-spiradoline, ICI 204448, and EMD 61753, and by the mixed-action /µ-agonists bremazocine and ethylketocyclazocine. The discriminative stimulus effects of enadoline were not reproduced by the µ-selective agonist morphine, the -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 -funaltrexamine (10.0 mg/kg) did not appreciably alter the dose-effect function for enadoline in any subject. However, the nonselective and -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 -receptor subtypes. The present results bolster the view that common discriminative stimulus effects of enadoline and other opioids are mediated by -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 -opioid receptors.