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Continuous opioid agonist treatment dose‐dependently regulates μ‐opioid receptors and dynamin‐2 in mouse spinal cord
Author(s) -
Zhang Qiuyu,
Purohit Vishal,
Yoburn Byron C.
Publication year - 2005
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20137
Subject(s) - etorphine , chemistry , spinal cord , opioid , agonist , morphine , endocrinology , medicine , pharmacology , opioid receptor , receptor , (+) naloxone , biology , neuroscience , biochemistry
Continuous opioid agonist treatment produces tolerance and in some cases μ opioid receptor (μOR) down‐regulation. Previous studies indicate that down‐regulation of μOR is more likely with high‐efficacy opioid agonists (e.g., etorphine), whereas lower efficacy agonists (e.g., morphine) do not regulate μOR density. It has been suggested that μOR down‐regulation may depend upon increases in Dynamin‐2 (DYN‐2) proteins. Therefore, the present study examined the effect of various infusion doses of etorphine on μOR density, DYN‐2 protein, and DYN‐2 mRNA abundance in mouse spinal cord. Mice were implanted sc with an osmotic pump that infused etorphine (50–250 μg/kg/day). Controls were implanted with inert placebo pellets. At the end of 7 days, mice were sacrificed, spinal cord removed and processed for radioligand binding, quantitative Western blotting, or RT‐PCR assay. Results indicate that etorphine induced dose‐dependent regulation of μOR density, DYN‐2 proteins, and mRNA abundance in mouse spinal cord. Higher infusion doses significantly down‐regulated μOR density, increased DYN‐2 protein abundance, and decreased DYN‐2 mRNA. Analysis of these results indicated a significant correlation between μOR down‐regulation and DYN‐2 abundance in mouse spinal cord. Taken together, μOR regulation may depend on changes in DYN‐2 abundance induced by high‐efficacy opioid agonists in mouse spinal cord. Synapse 56:123–128, 2005. © 2005 Wiley‐Liss, Inc.