CHRONIC OPIOID ANTAGONIST ADMINISTRATION UP-REGULATES MU-OPIOID RECEPTOR-BINDING WITHOUT ALTERING MU-OPIOID RECEPTOR MESSENGER-RNA LEVELS

Chronic administration of opioid antagonists has been shown to increas e radioligand binding to brain opioid receptors. The present study was conducted to determine whether chronic exposure to the opioid antagon ist naltrexone would similarly increase mu opioid receptor gene expres sion as measured by mRNA levels. Male Sprague-Dawley rats were adminis tered 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 wit h naltrexone as compared with saline-treated control animals. However, mu opioid receptor mRNA content determined by a solution hybridizatio n RNase protection assay was not significantly altered in any brain re gion 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.