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Chronic morphine and naltrexone fail to modify mu-opioid receptor mRNA levels in the rat brain
M P Castelli1, M Melis, M Mameli
1B.B. Brodie' Department of Neuroscience, University of Cagliari, Italy.
Abstract:
Previous radioligand-binding studies have reported conflicting results concerning the effect of chronic morphine administration on the regulation of mu-opioid receptor (MOR) density. On the other hand, chronic administration of an opioid antagonist, such as naltrexone, has been shown to increase the density of the MOR. In order to determine if the changes in the MOR are associated with alterations in receptor mRNA levels, we investigated MOR gene expression following chronic treatment with morphine and/or naltrexone. MOR mRNA levels, determined by the ribonuclease protection assay (RPA), were unchanged with respect to control during chronic morphine treatment and morphine withdrawal in each of the analysed brain areas. Furthermore, chronic administration of naltrexone did not result in changes of MOR mRNA levels in rat striatum of naive and morphine-dependent rats, suggesting that the up-regulation of the MOR density, at least in this tissue, is not regulated at transcriptional level.
Insights
Chronic morphine and naltrexone treatments did not alter mu-opioid receptor (MOR) mRNA levels in rats. This suggests that observed changes in MOR density are not regulated at the gene expression level.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Conflicting results exist regarding chronic morphine's effect on mu-opioid receptor (MOR) density.
- Opioid antagonists like naltrexone have been shown to increase MOR density.
Purpose of the Study:
- To investigate mu-opioid receptor (MOR) gene expression following chronic morphine and/or naltrexone treatment.
- To determine if changes in MOR density are linked to alterations in receptor mRNA levels.
Main Methods:
- Utilized ribonuclease protection assay (RPA) to measure MOR mRNA levels.
- Analyzed MOR gene expression in various rat brain areas after chronic morphine and naltrexone administration.
Main Results:
- MOR mRNA levels remained unchanged during chronic morphine treatment and withdrawal.
- Naltrexone administration did not alter MOR mRNA levels in rat striatum.
- No changes in MOR mRNA were observed in naive or morphine-dependent rats.
Conclusions:
- Mu-opioid receptor (MOR) density up-regulation is not regulated at the transcriptional level in rat striatum.
- Findings indicate post-transcriptional mechanisms may underlie MOR density changes in response to opioid treatment.