Chronic opioid antagonist administration upregulates mu opioid receptor binding without altering mu opioid receptor mRNA levels

Brain Res Mol Brain Res. 1995 Nov;33(2):351-5. doi: 10.1016/0169-328x(95)00143-g.


Chronic administration of opioid antagonists has been shown to increase radioligand binding to brain opioid receptors. The present study was conducted to determine whether chronic exposure to the opioid antagonist naltrexone would similarly increase mu opioid receptor gene expression as measured by mRNA levels. Male Sprague-Dawley rats were administered naltrexone, 7-8 mg/kg/day, or saline by osmotic minipumps for 7 days. As expected, the density of mu opioid receptor binding sites was significantly higher in the brains of animals treated chronically with naltrexone as compared with saline-treated control animals. However, mu opioid receptor mRNA content determined by a solution hybridization RNase protection assay was not significantly altered in any brain region investigated. These results indicate that the upregulation of mu opioid receptors as measured by radioligand binding is not accompanied by increased levels of mu receptor mRNA.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain / metabolism*
  • Cell Membrane / metabolism
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Enkephalins / metabolism
  • Gene Expression*
  • Kinetics
  • Male
  • Naltrexone / pharmacology*
  • Narcotic Antagonists / pharmacology*
  • Organ Specificity
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid, mu / biosynthesis
  • Receptors, Opioid, mu / metabolism*
  • Reference Values
  • Up-Regulation


  • Enkephalins
  • Narcotic Antagonists
  • RNA, Messenger
  • Receptors, Opioid, mu
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Naltrexone