U-50, 488, saline and naltrexone discrimination in U-50, 488-treated pigeons.
Pigeons treated with 10.0mg/kg/day of U-50,488 discriminated among intramuscular (i.m.) injections of U-50,488 (10mg/kg), saline, and naltrexone (0.178mg/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 0.032mg/kg of naltrexone, >/=90% on the U-50,488 key at doses larger than 3.2mg/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.
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Medical Center, New Orleans, LA 70119, USA.
C.P.
CP
France
J.H.
JH
Woods