ArticleThe Journal of pharmacology and experimental therapeutics2011
A novel knock-in mouse reveals mechanistically distinct forms of morphine tolerance.
Article in The Journal of pharmacology and experimental therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Lysosomal down-regulation of the mu opioid receptor is opposed by the Retromer complex.Science advances · 2026Article
- Differential Effects of a Novel Opioid Ligand UTA1003 on Antinociceptive Tolerance and Motor Behaviour.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Alternatively spliced mu opioid receptor C termini impact the diverse actions of morphine.The Journal of clinical investigation · 2017Article
- Article
- Real-time imaging of mu opioid receptors by total internal reflection fluorescence microscopy.Methods in molecular biology (Clifton, N.J.) · 2015Article
- Morphine desensitization and cellular tolerance are distinguished in rat locus ceruleus neurons.Molecular pharmacology · 2012Article
- Review
- In vivo visualization of delta opioid receptors upon physiological activation uncovers a distinct internalization profile.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Fast modulation of μ-opioid receptor (MOR) recycling is mediated by receptor agonists.The Journal of biological chemistry · 2012Article
- Chronic methadone treatment shows a better cost/benefit ratio than chronic morphine in mice.The Journal of pharmacology and experimental therapeutics · 2012Article
- Quantitative encoding of the effect of a partial agonist on individual opioid receptors by multisite phosphorylation and threshold detection.Science signaling · 2011Article
- Clinical opioids differentially induce co-internalization of μ- and δ-opioid receptors.Molecular painArticle
- Effects of microRNA-223 on morphine analgesic tolerance by targeting NLRP3 in a rat model of neuropathic pain.Molecular painArticle
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The role of μ-opioid receptor (MOR) down-regulation in opioid tolerance remains controversial. In this study, we used a novel knock-in mouse to examine how changing the extent of MOR down-regulation alters the development of morphine tolerance. These mice express a mutant MOR, degrading MOR (DMOR), that differs from the wild-type (WT) MOR in two ways: 1) unlike the recycling WT MOR, the mutant DMOR is targeted for degradation after its internalization, thus facilitating down-regulation; and 2) unlike the WT MOR, DMOR is efficiently internalized in response to morphine activation. We found that both WT MOR and DMOR mice develop tolerance to morphine, but DMOR mice exhibit a more rapid onset of tolerance and show receptor down-regulation. WT MOR mice develop morphine tolerance more slowly but even once profoundly tolerant show no receptor down-regulation. Furthermore, WT mice show significantly more morphine dependence than DMOR mice after long-term treatment as indicated by withdrawal. Taken together these data indicate that tolerance mediated by receptor down-regulation manifests differently both at the behavioral and biochemical level than does the actual morphine tolerance that occurs in WT mice and that loss of receptor function is not a major contributor to morphine tolerance in WT MOR mice.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.