Effects of opioids in morphine-treated pigeons trained to discriminate among morphine, the low-efficacy agonist nalbuphine, and saline.
In opioid-dependent subjects, the low-efficacy mu 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 kappa 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 micro agonist nalbuphine in morphine-treated pigeons are similar to those of other low-efficacy agonists, naltrexone, and the termination of daily morphine treatment.
Walker
Ellen A
EA
Department of Psychology, University of North Carolina at Chapel Hill, USA. ellen.walker@temple.edu
Picker
Mitchell J
MJ
Granger
Arthur
A
Dykstra
Linda A
LA
D000818:Animals; D010856:Columbidae; D003216:Conditioning, Operant / Q000187:drug effects; D004193:Discrimination Learning / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D009020:Morphine / Q000008:administration & dosage*; D009021:Morphine Dependence / Q000503:physiopathology; D009266:Nalbuphine / Q000008:administration & dosage*; D009294:Narcotics / Q000494:pharmacology*; D012965:Sodium Chloride / Q000008:administration & dosage
D009294:Narcotics; D012965:Sodium Chloride; D009020:Morphine; D009266:Nalbuphine