Discriminative stimulus effects of nalbuphine in rhesus monkeys
Three rhesus monkeys discriminated between 0.178 mg/kg of nalbuphine and saline while responding under a fixed-ratio 5 schedule of stimulus-shock termination. Nalbuphine produced dose-related increases in drug-lever responding with > or = 90% of responses occurring on the drug lever at doses larg...
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Published in | The Journal of pharmacology and experimental therapeutics Vol. 276; no. 2; pp. 523 - 531 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Pharmacology and Experimental Therapeutics
01.02.1996
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Subjects | |
Online Access | Get full text |
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Summary: | Three rhesus monkeys discriminated between 0.178 mg/kg of nalbuphine and saline while responding under a fixed-ratio 5 schedule
of stimulus-shock termination. Nalbuphine produced dose-related increases in drug-lever responding with > or = 90% of responses
occurring on the drug lever at doses larger than 0.1 mg/kg. The duration of action of the discriminative stimulus effects
of nalbuphine was less than 5.25 hr. Rank order potency of compounds that substituted for the nalbuphine discriminative stimulus
(i.e., > or = 90% responding on the nalbuphine lever) in all three subjects was fentanyl > butorphanol > methadone > morphine.
Compounds that did not substitute completely in all monkeys included the kappa agonists ethylketocyclazocine, enadoline, spiradoline
and U-50,488 and the nonopioids cocaine, d-amphetamine, clonidine, ketamine and phencyclidine. Naltrexone antagonized the
discriminative stimulus effects of nalbuphine, shifting the nalbuphine dose-effect curve in a manner that was consistent with
mu receptor mediation. Results from the current study demonstrate that, in rhesus monkeys, the discriminative stimulus effects
of nalbuphine are mediated by mu opioid receptors. Although there is evidence suggesting that nalbuphine has kappa agonist
effects (e.g., subjective effects in humans), results from several studies, including the current study, strongly suggest
that in rhesus monkeys nalbuphine does not exert agonist actions at kappa receptors. Moreover, these data indicate that differences
in behavioral effects between nalbuphine and prototypic mu opioids (e.g., morphine) probably result from differences in activity
(e.g., efficacy) at mu receptors rather than any kappa agonist actions of nalbuphine. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0022-3565 1521-0103 |