Comparison of the discriminative stimulus properties of U50,488 and morphine in pigeons

Pigeons were trained to discriminate a dose of either 4.2 mg/kg of U50,488 or 1.0 mg/kg of morphine from water using a two-key drug discrimination procedure. In U50,488-trained pigeons, the kappa agonist bremazocine occasioned drug-appropriate responding during substitution tests, whereas ethylketocyclazocine and ketocyclazocine occasioned intermediate levels of drug-appropriate responding up to and including doses that markedly suppressed response rates. The mu agonists morphine, l-methadone and fentanyl produced responding predominantly on the water-appropriate key. In morphine-trained pigeons, l-methadone, fentanyl, ethylketocyclazocine and ketocyclazocine, but not U50,488 and bremazocine, occasioned drug-appropriate responding. Nonopioid compounds, such as d-amphetamine, pentobarbital, phencyclidine and (+)-SKF 10,047 produced responding predominantly on the water-appropriate key in both U50,488- and morphine-trained pigeons. During tests of antagonism, a 0.1 and 1.0 mg/kg dose of naloxone antagonized completely the discriminative stimulus properties of the training dose of U50,488 and morphine, respectively. In addition, morphine displayed a substantially longer duration of action than U50,488, in that intermediate levels of drug-appropriate responding were evident as long as 4 hr after the administration of morphine and only 1 hr after the administration of U50,488. Over a period of approximately 8 months, the dose-effect curves for the discriminative stimulus properties of both drugs were unchanged. The present findings illustrate further the unique behavioral response of pigeons to the discriminative stimulus properties of the kappa agonists, and establishes that pigeons can discriminate between mu and some kappa agonists.