OPIOID ANTAGONIST-INDUCED RECEPTOR UP-REGULATION - EFFECTS OF CONCURRENT AGONIST ADMINISTRATION

The present study examined whether opioid antagonist-induced receptor upregulation could be antagonized by simultaneous treatment with opioi d agonists. Mice were treated concurrently with opioid agonists (morph ine, fentanyl, etorphine) and antagonists (naloxone, naltrexone) over a period of 7-8 days. Concurrent morphine (1 or 4, 75mg SC implanted p ellets), fentanyl (5.0mgkg/day, infusion) or etorphine (0.25mg/kg/day, infusion) administration were unable to inhibit upregulation of mu op ioid (DAMGO) receptors by either naloxone (1mg/kg/day, infusion) or na ltrexone (1.5mg 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-indu ced upregulation is a robust, receptor-mediated phenomenon.