Regulation of the mu-opioid receptor gene by opioid analgesic drugs has not been observed in @entity35 and @entity19 following in vivo treatments that produce tolerance. Although in vivo heterologous regulation of mu-opioid receptor mRNA by non-opioid compounds has been reported, the failure to observe changes in mu-opioid receptor mRNA levels in vivo after treatment with opioid agonists raised the possibility that in vivo homologous regulation by agonists may not occur. Therefore, in the present study, the effect of a high intrinsic efficacy opioid receptor agonist on opioid receptor density, gene expression and tolerance was determined. @entity19 were infused with @entity7240 for 7 days using an osmotic minipump, then the pump was removed and studies conducted 16-168 h later. @entity7240 (50-250 microg/kg/day) infusion produced significant dose-dependent tolerance to the analgesic (tailflick) effects of @entity7240 , as well as dose-dependent mu-opioid receptor downregulation in brain at 16 h following the end of the infusion. Mu-opioid receptor density returned to control levels over a 168 h period following the end of @entity7240 (250 microg/kg/day) infusion. Similarly, the magnitude of tolerance decreased over the same period. Evaluation of changes in brain mu-opioid receptor mRNA 16 h following @entity7240 infusion indicated that there was dose-dependent increase in steady-state levels, with no significant change in @entity26637 mRNA. The increase in mu-opioid receptor mRNA was approximately 55-65% over control at the highest @entity7240 infusion dose. Mu-opioid receptor mRNA returned to control levels over a 168 h period following the end of @entity7240 (250 microg/kg/day) infusion. These data suggest that the increase in mu-opioid receptor mRNA following the termination of @entity7240 treatment may drive the recovery of mu-opioid receptors. These data are the first demonstration of in vivo homologous regulation of mu-opioid receptor gene expression in the @entity19 by an opioid receptor agonist that produces tolerance and receptor downregulation.

In vivo homologous regulation of mu-opioid receptor gene expression in the XXXX .

@entity35 :: ('10116', 'Species') :: ['rats'] @entity26637 :: ('14433(Tax:10090)', 'Gene') :: ['GAPDH'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse', 'Mice'] @entity7240 :: ('MESH:D005048', 'Chemical') :: ['etorphine', 'Etorphine']
@entity19 :: (10090,Species) :: ['mouse']
