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 intramuscular (i.m.) injections of U-50,488 (10 mg/kg), saline, and naltrexone (0.178 mg/kg), while responding under a fixed-ratio 20 schedule of food presentation. Training compounds occasioned responding on the appropriate keys with pigeons responding ≥ 90% on the naltrexone key at doses larger than 0.032 mg/kg of naltrexone, ≥ 90% on the U-50,488 key at doses larger than 3.2 mg/kg of U-50,488, and ≥ 90% on the saline key after saline. Several opioid agonists and antagonists were studied for their discriminative stimulus effects. None of the compounds substituted completely (≥ 90%) for either training compound in all pigeons (n = 5); however, bremazocine substituted completely for U-50,488 in three out of five pigeons. Compounds with opioid antagonist actions under other conditions substituted for naltrexone in some subjects: levallorphan, two out of five; nalbuphine, one out of five; 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 were studied daily after injections of saline, responding occurred predominantly on the saline key; the absence of naltrexone key responding after termination of U-50,488 treatment suggests that this dosing regimen was not adequate for the development of dependence, or that the discriminative stimulus effects of abstinence-induced withdrawal were qualitatively different from the discriminative stimulus effects of naltrexone under these conditions.