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, 1.8mg/kg morphine, and 10mg/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 pA(2) 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.
Department of Psychology, Wayne State University, Detroit, Michigan 48202, USA.
S.A.
SA
Vanecek
A.M.
AM
Young