Opioid antagonist-induced receptor upregulation: Effects of concurrent agonist administration

• Published in: Brain research bulletin Vol. 33; no. 2; pp. 237 - 240
• Main Authors: Yoburn, Byron C., Duttaroy, Alokesh, Shah, Sukrut, Davis, Trong
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 1994
• Subjects: Animals; Brain - metabolism; Drug Combinations; Enkephalin, Ala-MePhe-Gly; Enkephalins - pharmacology; Etorphine; Etorphine - pharmacology; Fentanyl; Fentanyl - administration & dosage; Male; Mice; Morphine; Morphine - administration & dosage; Naloxone; Naloxone - pharmacology; Naltrexone; Naltrexone - pharmacology; Narcotic Antagonists - pharmacology; Opioid agonists; Opioid antagonists; Opioid receptors; Receptors, Opioid, mu - metabolism; Up-Regulation - drug effects; Upregulation μ opioid receptors; Naloxone; Opioid receptors; Opioid agonists; Etorphine; Fentanyl; Morphine; Upregulation μ opioid receptors; Opioid antagonists; Naltrexone
• ISSN: 0361-9230; 1873-2747
• DOI: 10.1016/0361-9230(94)90259-3

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, 75mg SC implanted pellets), fentanyl (5.0mgkg/day, infusion) or etorphine (0.25mg/kg/day, infusion) administration were unable to inhibit upregulation of μ opioid (DAMGO) receptors by either naloxone (1mg/kg/day, infusion) or naltrexone (15mg or 2mg SC implanted pellet). Only a very high infusion dose of etorphine (10mg/kg/day) inhibited upregulation by naltrexone (2mg SC implanted pellet). These results indicate that antagonist-induced upregulation is a robust, receptor-mediated phenomenon.