TY - JOUR
T1 - Differential tolerance to antinociceptive effects of μ opioids during repeated treatment with etonitazene, morphine, or buprenorphine in rats
AU - Walker, Ellen A.
AU - Young, Alice M.
PY - 2001
Y1 - 2001
N2 - Rationale: Repeated treatment experiments with high and low efficacy agonists provide critical insight into possible mechanisms underlying development of opioid tolerance. Objective: Experiments in a tail-withdrawal assay tested the hypothesis that magnitude of tolerance to antinociceptive effects is inversely related to agonist relative efficacy in rats intermittently treated with etonitazene, morphine, or buprenorphine. Methods: The antinociceptive effects of five μ opioid agonists were tested in male, Sprague-Dawley rats in a warm-water tail-withdrawal assay. To induce tolerance, escalating doses of the higher efficacy agonist etonitazene, the high efficacy agonist morphine, or the lower efficacy agonist buprenorphine were administered twice daily for 2-8 weeks. Results: Etonitazene, etorphine, morphine, buprenorphine, and GPA 1657 [(1)-β-2′-hydroxy-2, 9-dimethyl-5-phenyl-6, 7-benzomorphan] produced dose-dependent increases in tail-withdrawal latency until 100% maximum possible effect (%MPE) was obtained. Treatment with escalating doses of etonitazene, morphine, or buprenorphine produced greater tolerance to the lower efficacy agonists buprenorphine and GPA 1657 than to the higher efficacy agonists etonitazene, etorphine, and morphine. Treatment with buprenorphine, a lower efficacy agonist, produced greater tolerance than did treatment with equivalent doses of the higher efficacy agonists morphine or etonitazene. Conclusions: Taken together, these data suggest that magnitude of antinociceptive tolerance is inversely related to relative efficacy of μ agonists, with lower efficacy agonists being more susceptible to tolerance than are higher efficacy agonists under these intermittent dosing conditions.
AB - Rationale: Repeated treatment experiments with high and low efficacy agonists provide critical insight into possible mechanisms underlying development of opioid tolerance. Objective: Experiments in a tail-withdrawal assay tested the hypothesis that magnitude of tolerance to antinociceptive effects is inversely related to agonist relative efficacy in rats intermittently treated with etonitazene, morphine, or buprenorphine. Methods: The antinociceptive effects of five μ opioid agonists were tested in male, Sprague-Dawley rats in a warm-water tail-withdrawal assay. To induce tolerance, escalating doses of the higher efficacy agonist etonitazene, the high efficacy agonist morphine, or the lower efficacy agonist buprenorphine were administered twice daily for 2-8 weeks. Results: Etonitazene, etorphine, morphine, buprenorphine, and GPA 1657 [(1)-β-2′-hydroxy-2, 9-dimethyl-5-phenyl-6, 7-benzomorphan] produced dose-dependent increases in tail-withdrawal latency until 100% maximum possible effect (%MPE) was obtained. Treatment with escalating doses of etonitazene, morphine, or buprenorphine produced greater tolerance to the lower efficacy agonists buprenorphine and GPA 1657 than to the higher efficacy agonists etonitazene, etorphine, and morphine. Treatment with buprenorphine, a lower efficacy agonist, produced greater tolerance than did treatment with equivalent doses of the higher efficacy agonists morphine or etonitazene. Conclusions: Taken together, these data suggest that magnitude of antinociceptive tolerance is inversely related to relative efficacy of μ agonists, with lower efficacy agonists being more susceptible to tolerance than are higher efficacy agonists under these intermittent dosing conditions.
KW - Buprenorphine
KW - Efficacy
KW - Etonitazene
KW - Etorphine
KW - Morphine
KW - Rat
KW - Tolerance
UR - http://www.scopus.com/inward/record.url?scp=0035111517&partnerID=8YFLogxK
U2 - 10.1007/s002130000620
DO - 10.1007/s002130000620
M3 - Article
C2 - 11314675
AN - SCOPUS:0035111517
SN - 0033-3158
VL - 154
SP - 131
EP - 142
JO - Psychopharmacology
JF - Psychopharmacology
IS - 2
ER -