U-50,488, SALINE AND NALTREXONE DISCRIMINATION IN U-50,488-TREATED PIGEONS

Pigeons treated with 10.0 mg/kg/day of U-50,488 discriminated among in tramuscular (i.m.) injections of U-50,488 (10 mg/kg), saline, and nalt rexone (0.178 mg/kg), while responding under a fixed-ratio 20 schedule of food presentation. Training com pounds occasioned responding on th e appropriate keys with pigeons responding greater-than-or-equal-to 90 % on the naltrexone key at doses larger than 0.032 mg/kg of naltrexone , greater-than-or-equal-to 90% on the U-50,488 key at doses larger tha n 3.2 mg/kg of U-50,488, and greater-than-or-equal-to 90% on the salin e key after saline. Several opioid agonists and antagonists were studi ed for their discriminative stimulus effects. None of the compounds su bstituted completely (greater-than-or-equal-to 90%) for either trainin g compound in all pigeons (n = 5); however, bremazocine substituted co mpletely for U-50,488 in three out of five pigeons. Compounds with opi oid antagonist actions under other conditions substituted for naltrexo ne in some subjects: levallorphan, two out of rive; nalbuphine, one ou t of rive; nalorphine, two out of five; and quadazocine, three out of four. Morphine did not substitute for naltrexone or U-50,488 in any of the subjects. When U-50,488 treatment was terminated and subjects wer e studied daily after injections of saline, responding occurred predom inantly on the saline key; the absence of naltrexone key responding af ter termination of U-50,488 treatment suggests that this dosing regime n was not adequate for the development of dependence, or that the disc riminative stimulus effects of abstinence-induced withdrawal were qual itatively different from the discriminative stimulus effects of naltre xone under these conditions.