scholarly journals Mu opioid receptor and orexin/hypocretin mRNA levels in the lateral hypothalamus and striatum are enhanced by morphine withdrawal

2006 ◽  
Vol 191 (1) ◽  
pp. 137-145 ◽  
Author(s):  
Yan Zhou ◽  
Jacob Bendor ◽  
Lauren Hofmann ◽  
Matthew Randesi ◽  
Ann Ho ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Lateral Hypothalamus ◽  
Brain Regions ◽  
Mu Opioid Receptor ◽  
Morphine Withdrawal ◽  
Mrna Levels ◽  
Chronic Morphine ◽  
Mu Opioid ◽  
Morphine Administration ◽  
Related Stress

In this study, we investigated the effects of acute morphine administration, chronic intermittent escalating-dose morphine administration and spontaneous withdrawal from chronic morphine on mRNA levels of mu opioid receptor (MOP-r), and the opioid peptides pro-opiomelanocortin (POMC) and preprodynorphin (ppDyn) in several key brain regions of the rat, associated with drug reward and motivated behaviors: lateral hypothalamus (lat.hyp), nucleus accumbens (NAc) core, amygdala, and caudate–putamen (CPu). There was no effect on MOP-r mRNA levels in these brain regions 30 min after either a single injection of morphine (10 mg/kg, i.p.) or chronic intermittent escalating-dose morphine (from 7.5 mg/kg per day on day 1 up to 120 mg/kg per day on day 10). Activation of the stress-responsive hypothalamic–pituitary–adrenal axis by 12 h withdrawal from chronic morphine was confirmed; both POMC mRNA levels in the anterior pituitary and plasma adrenocorticotropic hormone levels were significantly elevated. Under this withdrawal-related stress condition, there was an increase in MOP-r mRNA levels in the lat.hyp, NAc core, and CPu. Recent studies have demonstrated a novel role for the lat.hyp orexin (or hypocretin) activation in both drug-related positive rewarding, and withdrawal effects. Around 50% of lat.hyp orexin neurons express MOP-r. Therefore, we also examined the levels of lat.hyp orexin mRNA, and found them increased in morphine withdrawal, whereas there was no change in levels of the lat.hyp ppDyn mRNA, a gene coexpressed with the lat.hyp orexin. Our results show that there is an increase in MOP-r gene expression in a region-specific manner during morphine withdrawal, and support the hypothesis that increased lat.hyp orexin activity plays a role in morphine-withdrawal-related behaviors.

scholarly journals Stabilization of morphine tolerance with long-term dosing: Association with selective upregulation of mu-opioid receptor splice variant mRNAs

2014 ◽  
Vol 112 (1) ◽  
pp. 279-284 ◽  
Author(s):  
Jin Xu ◽  
Andrew J. Faskowitz ◽  
Grace C. Rossi ◽  
Mingming Xu ◽  
Zhigang Lu ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Splice Variants ◽  
Chronic Administration ◽  
Morphine Tolerance ◽  
Brain Regions ◽  
Progressive Increase ◽  
Mu Opioid Receptor ◽  
Mrna Levels ◽  
Chronic Morphine ◽  
Mu Opioid

Chronic morphine administration is associated with the development of tolerance, both clinically and in animal models. Many assume that tolerance is a continually progressive response to chronic opioid dosing. However, clinicians have long appreciated the ability to manage cancer pain in patients for months on stable opioid doses, implying that extended dosing may eventually result in a steady state in which the degree of tolerance remains constant despite the continued administration of a fixed morphine dose. Preclinical animal studies have used short-term paradigms, typically a week or less, whereas the clinical experience is based upon months of treatment. Chronic administration of different fixed morphine doses produced a progressive increase in the ED50 that peaked at 3 wk in mice, consistent with prior results at shorter times. Continued morphine dosing beyond 3 wk revealed stabilization of the level of tolerance for up to 6 wk with no further increase in the ED50. The degree of tolerance at all time points was dependent upon the dose of morphine. The mRNA levels for the various mu opioid receptor splice variants were assessed to determine whether stabilization of morphine tolerance was associated with changes in their levels. After 6 wk of treatment, mRNA levels of the variants increased as much as 300-fold for selected variants in specific brain regions. These findings reconcile preclinical and clinical observations regarding the development of morphine tolerance.

scholarly journals EFFECTS OF ZAMZAM WATER AND METHADONE ON THE EXPRESSION OF MU-OPIOID RECEPTOR-1 GENE IN MORPHINE-DEPENDENT RATS AFTER CHRONIC MORPHINE ADMINISTRATION

2018 ◽  
Vol 15 (2) ◽  
pp. 19 ◽  
Author(s):  
Shariff Halim ◽  
Nasir Mohamad ◽  
Nor Hidayah Abu Bakar ◽  
Rohayah Husain ◽  
Khairi Che Mat ◽  
...  
Keyword(s):  
Gene Expression ◽  
Opioid Receptor ◽  
Mineral Water ◽  
Tap Water ◽  
Mu Opioid Receptor ◽  
Sodium Ion ◽  
Ion Concentration ◽  
Chronic Morphine ◽  
Mu Opioid ◽  
Morphine Administration

Background: Sodium ion is an essential ion that is implicated in many physiological functions. Recently, sodium ion was reported to facilitate the activation of Mu-Opioid Receptor (MOR) by binding at the allosteric site of the MOR. Zamzam water is water originated from Mecca. Couple of studies proved that Zamzam water has the therapeutic effect owing to its mineral. In this study, we want to determine the ion concentration of Zamzam water and then to investigate the effects of Zamzam water and co-treatment with methadone on the regulation of MOR-1gene after chronic morphine administration. Materials and Methods: Zamzam water, tap water and normal mineral water were analyzed using Ion chromatography. Meanwhile, in animal study, 50 male Sprague Dawley rats were randomly divided into five groups. All group of rat were made dependence on morphine using intraperitoneal injection except for normal group. Morphine dependent rats then were treated with methadone, Zamzam water and co-treatment methadone with Zamzam water for thirty days, respectively. The Ventral Tegmental Area (VTA) of rat’s brain was dissected and subjected to real-time quantitative RT-PCR to determine the regulation of MOR-1 gene expression. The obtained data were analyzed using SPSS v.11 software, and one-way ANOVA followed by Tukey’s Post-test. Results: The data obtained showed that Zamzam water is significantly high in ion concentration compared to tap water and normal mineral water. Besides, the result from gene expression analysis showed co-treatment Zamzam water and methadone significantly prevented the downregulation of MOR as compared to methadone and Zamzam water treatment alone (P

Cocaine modulates mu-opioid receptor mRNA but not c-fos mRNA levels in primary cortical astrocytes

2002 ◽  
Vol 58 (3) ◽  
pp. 285-288 ◽  
Author(s):  
Eugene D Festa ◽  
Christine Cecala ◽  
Vanya Quinones-Jenab ◽  
Shirzad Jenab
Keyword(s):  
Opioid Receptor ◽  
Mu Opioid Receptor ◽  
Mrna Levels ◽  
Mu Opioid ◽  
Receptor Mrna ◽  
Cortical Astrocytes

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

1995 ◽  
Vol 33 (2) ◽  
pp. 351-355 ◽  
Author(s):  
Ellen M. Unterwald ◽  
Joshua M. Rubenfeld ◽  
Yasuo Imai ◽  
Jia-Bei Wang ◽  
George R. Uhl ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Receptor Binding ◽  
Mu Opioid Receptor ◽  
Opioid Antagonist ◽  
Mrna Levels ◽  
Mu Opioid ◽  
Receptor Mrna ◽  
Opioid Receptor Binding

Acute “binge” cocaine increases mu-opioid receptor mRNA levels in areas of the rat mesolimbic mesocortical dopamine system

1999 ◽  
Vol 48 (1) ◽  
pp. 109-112 ◽  
Author(s):  
Vadim Yuferov ◽  
Yan Zhou ◽  
Rudolph Spangler ◽  
Christopher E Maggos ◽  
Ann Ho ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Mu Opioid Receptor ◽  
Mrna Levels ◽  
Dopamine System ◽  
Mu Opioid ◽  
Receptor Mrna

MU OPIOID RECEPTOR (MOR-1) mRNA LEVELS ARE ALTERED IN MICE WITH DIFFERENTIAL ANALGESIC SENSITIVITY TO THE MU AGONIST DAMGO

Analgesia ◽  
1995 ◽  
Vol 1 (4) ◽  
pp. 498-501 ◽  
Author(s):  
B. Kest ◽  
M. Brodsky ◽  
B. Sadowski ◽  
J.S. Mogil ◽  
C.E. Inturrisi
Keyword(s):  
Opioid Receptor ◽  
Mu Opioid Receptor ◽  
Mrna Levels ◽  
Mu Opioid

Regulation of Mu Opioid Receptor mRNA Levels by Activation of Protein Kinase C in Human SH-SY5Y Neuroblastoma Cells 

1997 ◽  
Vol 87 (5) ◽  
pp. 1127-1138 ◽  
Author(s):  
Elizabeth K. Gies ◽  
Dawn M. Peters ◽  
Carol R. Gelb ◽  
Kathleen M. Knag ◽  
Robert A. Peterfreund
Keyword(s):  
Protein Synthesis ◽  
Neuropathic Pain ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Opioid Receptor ◽  
Mu Opioid Receptor ◽  
Mrna Levels ◽  
Mu Opioid ◽  
Receptor Mrna ◽  
Kinase C

Background The mu opioid receptor (MuOR) is a member of the superfamily of G protein-coupled receptors that mediates the analgesic actions of endogenous opioid peptides and the narcotic alkaloid derivatives of morphine. Activation and translocation of protein kinase C (PKC) by N-methyl-D-aspartate receptor stimulation correlates with resistance to opioid drugs in experimental states of neuropathic pain, but the cellular mechanisms of resistance have not been identified. One possibility is that PKC activation regulates MuOR mRNA expression and thus the ability to generate functional receptors. Using a human neuroblastoma cell line, the authors tested the hypothesis that phorbol ester activation of PKC regulates MuOR mRNA levels. Methods SH-SY5Y cells were maintained in a continuous monolayer culture and treated with phorbol esters or other agents before extraction of total cellular RNA. Slot-blot hybridization was used to measure the level of MuOR mRNA using 32P-labeled MuOR cDNA probes under high-stringency conditions. Autoradiograms were analyzed by scanning and densitometry. Results MuOR mRNA levels decreased in a dose- and time-dependent manner after tetradecanoyl phorbol acetate (TPA) was administered to activate PKC. The nadir, a level of approximately 50% of control, was at 2-8 h, followed by gradual recovery. The actions of TPA were blocked by pretreatment with the selective PKC inhibitor bisindolylmaleimide, but not by inhibition of protein synthesis with cycloheximide or anisomycin. The combination of TPA treatment and transcription inhibition with actinomycin D was associated with a transient increase in MuOR mRNA. Conclusions Mu opioid receptor mRNA levels are regulated by activation of PKC in a neuronal model. Protein kinase C effects which decrease MuOR mRNA levels appear largely independent of new protein synthesis, and cytotoxicity does not account for the findings. Plasticity of MuOR gene expression may contribute to variations in clinical responses to opioid analgesics in clinical states such as neuropathic pain.

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