TY - JOUR T1 - Effects of Opioids in Morphine-Treated Pigeons Trained to Discriminate among Morphine, the Low-Efficacy Agonist Nalbuphine, and Saline JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 150 LP - 158 DO - 10.1124/jpet.103.058503 VL - 310 IS - 1 AU - Ellen A. Walker AU - Mitchell J. Picker AU - Arthur Granger AU - Linda A. Dykstra Y1 - 2004/07/01 UR - http://jpet.aspetjournals.org/content/310/1/150.abstract N2 - In opioid-dependent subjects, the low-efficacy μ agonist nalbuphine generally precipitates withdrawal or withdrawal-like stimulus effects. To provide a more complete characterization of the discriminative stimulus effects of nalbuphine in opioid-treated subjects, seven White Carneux pigeons were treated daily with 10 mg/kg morphine i.m. and trained 6 h later to discriminate among 10 mg/kg morphine, 1.0 mg/kg nalbuphine, and saline by responding on one of three different keys. When tested, morphine produced morphine-key responding and nalbuphine produced nalbuphine-key responding. Replacing the daily morphine injection with saline produced nalbuphine-key responding, and this effect was reversed by the administration of morphine. In substitution tests with other compounds, the antagonists naltrexone (i.m.) and CTAP (d-Phe-Cys-Tyr-d-Tryp-Lys-Thr-Pen-Thr-NH2) (i.c.v.) produced nalbuphine-key responding. High-efficacy agonists fentanyl and etorphine produced morphine-key responding. The intermediate-efficacy agonists buprenorphine, dezocine, and butorphanol produced a pattern of morphine-, saline-, and/or nalbuphine-key responding that differed across individual pigeons. The lower efficacy agonists nalorphine and levallorphan produced predominantly nalbuphine-key responding. The κ agonists spiradoline and U50,488 [trans-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]cyclohexyl)benzeneacetamide methanesulfonate], the nonopioid d-amphetamine, and saline produced predominantly saline-key responding. Naltrexone and nalbuphine dose dependently reversed the morphine-key responding produced by the training dose of morphine. Together, these data suggest that the discriminative-stimulus effects of the low-efficacy μ agonist nalbuphine in morphine-treated pigeons are similar to those of other low-efficacy agonists, naltrexone, and the termination of daily morphine treatment. The American Society for Pharmacology and Experimental Therapeutics ER -