Three-choice discrimination in pigeons is based on relative efficacy differences among opioids

Rationale: Drug discrimination assays can provide important information on receptor selectivity and relative efficacy to guide the classification and characterization of opioid agonists. Objectives: A three-choice discriminat ion was established among high efficacy opioid agonist morphine, low effica cy opioid agonist nalbuphine, and saline to examine the conditions under wh ich differences in relative efficacy might serve as a basis for stimulus co ntrol. Methods: Seven White Carneau pigeons were trained to discriminate am ong 5.6 mg/kg nalbuphine, 3.2 mg/kg morphine, and saline under fixed ratio 30 (FR30) schedules of food reinforcement. Substitution and antagonism expe riments were then conducted with mu, kappa, and delta opioids and naltrexon e, respectively and the percent responding appropriate to the training stim uli was determined. Results Low, intermediate, and high doses of morphine p roduced greater than or equal to 80% saline-, greater than or equal to 60% nalbuphine-, and greater than or equal to 96% morphine-appropriate ate resp onding, respectively. Low and high doses of nalbuphine produced greater tha n or equal to 80% saline- and nalbuphine-appropriate responding, respective ly. In substitution tests, low doses of fentanyl and etorphine produced par tial nalbuphine-appropriate responding (20-60%) and high doses produced gre ater than or equal to 60-80% morphine-appropriate responding. Intermediate doses of buprenorphine and dezocine produced greater than or equal to 60-80 % nalbuphine-appropriate responding and high doses produced greater than or equal to 80% morphine-appropriate responding. The lower efficacy agonists butorphanol, nalorphine, and levallorphan produced greater than or equal to 40-80% nalbuphine-appropriate responding. The kappa- agonists spiradoline and U50,488 produced approximately greater than or equal to 50% nalbuphine- appropriate responding whereas d-amphetamine, saline, and delta agonists BW 373U86 and SNC 80 produced greater than or equal to 80% saline-appropriate responding. Naltrexone produced greater than or equal to 80% saline-appropr iate responding and reversed the stimulus effects of morphine and nalbuphin e. Conclusions: The discrimination between morphine and nalbuphine in pigeo ns is predominantly based on the relative efficacy differences between morp hine, a higher-efficacy mu agonist and nalbuphine, a lower-efficacy mu agon ist.