Opioid agonist efficacy predicts the magnitude of tolerance and the regulation of μ-opioid receptors and dynamin-2

摘要: It has been proposed that opioid agonist efficacy may play a role in tolerance and the regulation of receptor density. To address this issue, present studies estimated vivo three agonists then examined changes spinal mu-opioid density following chronic treatment mouse. In addition, trafficking protein dynamin-2 were determined. evaluate efficacy, method irreversible alkylation was employed parameter tau estimated. Mice injected with antagonist clocinnamox (0.32-25.6 mg/kg, i.p), 24 h later, analgesic potency s.c. morphine, oxycodone etorphine Clocinnamox dose-dependently antagonized effects oxycodone. The shift to right dose-response curves greater for morphine compared highest dose reduced maximal effect oxycodone, but not etorphine. order calculated from these results etorphine>morphine>oxycodone. Other mice infused 7 days (10-150 mg/kg/day, s.c.) or (50-250 microg/kg/day, low (oxycodone) produced more than high (etorphine) at equi-effective infusion doses. saturation binding experiments, (morphine, oxycodone) did regulate receptors, while approximately 40% reduction Furthermore, increased abundance, produce any significant change abundance. Overall, data indicate less associated downregulation upregulation. Conversely, lower doses, Taken together, plays an important receptors proteins.