scholarly journals Mu-opioid receptor splice variants: sex-dependent regulation by chronic morphine

2014 ◽  
Vol 130 (6) ◽  
pp. 790-796 ◽  
Author(s):  
Vittorio Verzillo ◽  
Priyanka A. Madia ◽  
Nai-Jiang Liu ◽  
Sumita Chakrabarti ◽  
Alan R. Gintzler
Keyword(s):  
Opioid Receptor ◽  
Splice Variants ◽  
Mu Opioid Receptor ◽  
Chronic Morphine ◽  
Mu Opioid

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.

Morphine produces potent antinociception, sedation, and hypothermia in humanized mice expressing human mu-opioid receptor splice variants

Pain ◽  
2020 ◽  
Vol 161 (6) ◽  
pp. 1177-1190 ◽  
Author(s):  
Yi-Han Huang ◽  
Yu-Wei Wu ◽  
Jian-Ying Chuang ◽  
Yung-Chiao Chang ◽  
Hsiao-Fu Chang ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Splice Variants ◽  
Mu Opioid Receptor ◽  
Humanized Mice ◽  
Mu Opioid

scholarly journals Isolation and characterization of new exon 11-associated N-terminal splice variants of the human mu opioid receptor gene

2009 ◽  
Vol 108 (4) ◽  
pp. 962-972 ◽  
Author(s):  
Jin Xu ◽  
Mingming Xu ◽  
Yasmin L. Hurd ◽  
Gavril W. Pasternak ◽  
Ying-Xian Pan
Keyword(s):  
Opioid Receptor ◽  
Splice Variants ◽  
Receptor Gene ◽  
Mu Opioid Receptor ◽  
Mu Opioid ◽  
Isolation And Characterization ◽  
Exon 11

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.

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