Pharmacological characterization of an operant discrimination among two doses of morphine and saline in pigeons

A cumulative dose, multiple-trial test procedure was developed in eight pigeons trained to discriminate among saline, 1.8 mg/kg morphine, and 10 mg/kg morphine. Initially, single-trial tests were used to evaluate stimulus effects of acute doses of morphine. Next, the test procedure was altered so that cumulative doses were tested within a single session. Results from cumulative-dose tests of morphine were consistent with those from single-trial tests. The cumulative-dose test procedure was then used to characterize the high-dose and low-dose morphine training stimuli. The mu agonists etorphine, fentanyl, methadone and morphine dose-dependently evoked both low-dose and high-dose morphine-like effects, with a similar potency order (etorphine > fentanyl > methadone = morphine). In contrast, nalbuphine evoked only low-dose effects, consistent with low efficacy mu agonist activity. The kappa opiate U50,488H evoked saline-key responses, whereas the non-opiate ketamine evoked saline-key responses in the majority of pigeons, but high-dose and/or low-dose responding in others. Naltrexone dose-dependently antagonized both low-dose and high-dose stimulus effects of morphine, but not its rate-decreasing effects. Apparent pA₂ values for naltrexone were 7.2 for low-dose stimulus effects of morphine, and 7.4 for high-dose effects. These characteristics suggest that stimulus effects of both low and high training doses of morphine are mediated by common, presumably mu opioid, receptor populations.