Opioid antagonist-induced receptor upregulation: effects of concurrent agonist administration.
The present study examined whether opioid antagonist-induced receptor upregulation could be antagonized by simultaneous treatment with opioid agonists. Mice were treated concurrently with opioid agonists (morphine, fentanyl, etorphine) and antagonists (naloxone, naltrexone) over a period of 7-8 days. Concurrent morphine (1 or 4, 75 mg SC implanted pellets), fentanyl (5.0 mg/kg/day, infusion) or etorphine (0.25 mg/kg/day, infusion) administration were unable to inhibit upregulation of mu opioid (DAMGO) receptors by either naloxone (1 mg/kg/day, infusion) or naltrexone (15 mg or 2 mg SC implanted pellet). Only a very high infusion dose of etorphine (10 mg/kg/day) inhibited upregulation by naltrexone (2mg SC implanted pellet). These results indicate that antagonist-induced upregulation is a robust, receptor-mediated phenomenon.
Yoburn
B C
BC
Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St. John's University, Queens, NY 11439.
Duttaroy
A
A
Shah
S
S
Davis
T
T
D000818:Animals; D001921:Brain / Q000378:metabolism; D004338:Drug Combinations; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D005048:Etorphine / Q000494:pharmacology; D005283:Fentanyl / Q000008:administration & dosage; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects*
D004338:Drug Combinations; D004745:Enkephalins; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D005048:Etorphine; D009271:Naltrexone; D009020:Morphine; D005283:Fentanyl