scholarly journals Increased Abundance of Opioid Receptor Heteromers After Chronic Morphine Administration

2010 ◽  
Vol 3 (131) ◽  
pp. ra54-ra54 ◽  
Author(s):  
A. Gupta ◽  
J. Mulder ◽  
I. Gomes ◽  
R. Rozenfeld ◽  
I. Bushlin ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Chronic Morphine ◽  
Morphine Administration ◽  
Receptor Heteromers

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 On the G-Protein-Coupled Receptor Heteromers and Their Allosteric Receptor-Receptor Interactions in the Central Nervous System: Focus on Their Role in Pain Modulation

2013 ◽  
Vol 2013 ◽  
pp. 1-17 ◽  
Author(s):  
Dasiel O. Borroto-Escuela ◽  
Wilber Romero-Fernandez ◽  
Alicia Rivera ◽  
Kathleen Van Craenenbroeck ◽  
Alexander O. Tarakanov ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
G Protein ◽  
Opioid Receptor ◽  
Pain Modulation ◽  
Chronic Morphine ◽  
Receptor Heteromers ◽  
Receptor Interactions ◽  
The Central Nervous System

The modulatory role of allosteric receptor-receptor interactions in the pain pathways of the Central Nervous System and the peripheral nociceptors has become of increasing interest. As integrators of nociceptive and antinociceptive wiring and volume transmission signals, with a major role for the opioid receptor heteromers, they likely have an important role in the pain circuits and may be involved in acupuncture. The delta opioid receptor (DOR) exerts an antagonistic allosteric influence on the mu opioid receptor (MOR) function in a MOR-DOR heteromer. This heteromer contributes to morphine-induced tolerance and dependence, since it becomes abundant and develops a reduced G-protein-coupling with reduced signaling mainly operating viaβ-arrestin2 upon chronic morphine treatment. A DOR antagonist causes a return of the Gi/o binding and coupling to the heteromer and the biological actions of morphine. The gender- and ovarian steroid-dependent recruitment of spinal cord MOR/kappa opioid receptor (KOR) heterodimers enhances antinociceptive functions and if impaired could contribute to chronic pain states in women. MOR1D heterodimerizes with gastrin-releasing peptide receptor (GRPR) in the spinal cord, mediating morphine induced itch. Other mechanism for the antinociceptive actions of acupuncture along meridians may be that it enhances the cross-desensitization of the TRPA1 (chemical nociceptor)-TRPV1 (capsaicin receptor) heteromeric channel complexes within the nociceptor terminals located along these meridians. Selective ionotropic cannabinoids may also produce cross-desensitization of the TRPA1-TRPV1 heteromeric nociceptor channels by being negative allosteric modulators of these channels leading to antinociception and antihyperalgesia.

Chronic morphine administration results in tolerance to delta opioid receptor-mediated antinociception

Neuroscience ◽  
2006 ◽  
Vol 141 (2) ◽  
pp. 947-954 ◽  
Author(s):  
A.A.A. Pradhan ◽  
C. Siau ◽  
A. Constantin ◽  
P.B.S. Clarke
Keyword(s):  
Opioid Receptor ◽  
Delta Opioid Receptor ◽  
Chronic Morphine ◽  
Morphine Administration

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

scholarly journals Opioid receptor heteromers in analgesia

2012 ◽  
Vol 14 ◽  
Author(s):  
Cristina M. Costantino ◽  
Ivone Gomes ◽  
Steven D. Stockton ◽  
Maribel P. Lim ◽  
Lakshmi A. Devi
Keyword(s):  
Opioid Receptor ◽  
Opioid Receptors ◽  
Therapeutic Targets ◽  
Endogenous Opioid ◽  
Chronic Morphine ◽  
Receptor Complexes ◽  
Receptor Signalling ◽  
Receptor Heteromers ◽  
The Usa ◽  
Abused Drugs

Opiates such as morphine and fentanyl, a major class of analgesics used in the clinical management of pain, exert their effects through the activation of opioid receptors. Opioids are among the most commonly prescribed and frequently abused drugs in the USA; however, the prolonged use of opiates often leads to the development of tolerance and addiction. Although blockade of opioid receptors with antagonists such as naltrexone and naloxone can lessen addictive impulses and facilitate recovery from overdose, systemic disruption of endogenous opioid receptor signalling through the use of these antagonistic drugs can have severe side effects. In the light of these challenges, current efforts have focused on identifying new therapeutic targets that selectively and specifically modulate opioid receptor signalling and function so as to achieve analgesia without the adverse effects associated with chronic opiate use. We have previously reported that opioid receptors interact with each other to form heteromeric complexes and that these interactions affect morphine signalling. Since chronic morphine administration leads to an enhanced level of these heteromers, these opioid receptor heteromeric complexes represent novel therapeutic targets for the treatment of pain and opiate addiction. In this review, we discuss the role of heteromeric opioid receptor complexes with a focus on mu opioid receptor (MOR) and delta opioid receptor (DOR) heteromers. We also highlight the evidence for altered pharmacological properties of opioid ligands and changes in ligand function resulting from the heteromer formation.

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