TY - JOUR
T1 - Discriminative-stimulus effects of the low efficacy mu agonist nalbuphine
AU - Walker, E. A.
AU - Young, A. M.
N1 - Copyright:
Copyright 2004 Elsevier B.V., All rights reserved.
PY - 1993
Y1 - 1993
N2 - The discriminative stimulus effects of nalbuphine were studied in 15 male Sprague-Dawley rats trained to discriminate 3.2 mg/kg of nalbuphine from saline under a fixed-ratio 15 schedule of food delivery. Cumulative doses of nalbuphine produced nalbuphine lever responding at doses of 1.0 to 10 mg/kg and rate-suppressing effects at doses of 3.2 to 32 mg/kg. Experiments to evaluate the contribution of opioid receptor activity suggested that the stimulus effects of nalbuphine were mediated through mu systems, inasmuch as mu agonists (etorphine, fentanyl, morphine, buprenorphine, GPA 1657 and nalorphine) produced nalbuphine lever responding, whereas kappa agonists {EKC and U-50,488H (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl] benzeneacetamide methanesulfonate hydrate)} and nonopioids (d- pentazocine, d-amphetamine and ketamine) produced saline lever responding. dl-Pentazocine produced nalbuphine lever responding in one-half the rats tested. Both high and low efficacy agonists produced nalbuphine lever responding, but the antagonist naltrexone produced predominately saline lever responding. Increasing the training dose of nalbuphine by a 0.50 log unit failed to alter the potency of nalbuphine or any other compound to produce nalbuphine lever responding, suggesting that these training doses produce a maximum amount of stimulation at the mu receptor. Naltrexone antagonized the discriminative stimulus but not the rate-decreasing effects of nalbuphine, suggesting that only the discriminative stimulus effects of nalbuphine are mediated by a mu opioid mechanism. Nalbuphine appears to be a low efficacy agonist at the mu opioid receptor and can therefore be used as a too for testing hypotheses about efficacy in the drug discrimination procedure.
AB - The discriminative stimulus effects of nalbuphine were studied in 15 male Sprague-Dawley rats trained to discriminate 3.2 mg/kg of nalbuphine from saline under a fixed-ratio 15 schedule of food delivery. Cumulative doses of nalbuphine produced nalbuphine lever responding at doses of 1.0 to 10 mg/kg and rate-suppressing effects at doses of 3.2 to 32 mg/kg. Experiments to evaluate the contribution of opioid receptor activity suggested that the stimulus effects of nalbuphine were mediated through mu systems, inasmuch as mu agonists (etorphine, fentanyl, morphine, buprenorphine, GPA 1657 and nalorphine) produced nalbuphine lever responding, whereas kappa agonists {EKC and U-50,488H (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl] benzeneacetamide methanesulfonate hydrate)} and nonopioids (d- pentazocine, d-amphetamine and ketamine) produced saline lever responding. dl-Pentazocine produced nalbuphine lever responding in one-half the rats tested. Both high and low efficacy agonists produced nalbuphine lever responding, but the antagonist naltrexone produced predominately saline lever responding. Increasing the training dose of nalbuphine by a 0.50 log unit failed to alter the potency of nalbuphine or any other compound to produce nalbuphine lever responding, suggesting that these training doses produce a maximum amount of stimulation at the mu receptor. Naltrexone antagonized the discriminative stimulus but not the rate-decreasing effects of nalbuphine, suggesting that only the discriminative stimulus effects of nalbuphine are mediated by a mu opioid mechanism. Nalbuphine appears to be a low efficacy agonist at the mu opioid receptor and can therefore be used as a too for testing hypotheses about efficacy in the drug discrimination procedure.
UR - http://www.scopus.com/inward/record.url?scp=0027489954&partnerID=8YFLogxK
M3 - Article
C2 - 8229759
AN - SCOPUS:0027489954
VL - 267
SP - 322
EP - 330
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
SN - 0022-3565
IS - 1
ER -