ArticleMolecular pharmacology2012
Morphine desensitization and cellular tolerance are distinguished in rat locus ceruleus neurons.
Article in Molecular pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 51 citations in OpenAlex.
- Neuropeptides as transmitters and regulators of the locus coeruleus noradrenergic system.Pharmacological reviews · 2025Review
- Respiratory Depression Associated with Opioids: A Narrative Review.Current treatment options in oncology · 2024Review
- Chronic morphine treatment induces sex- and synapse-specific cellular tolerance on thalamo-cortical mu opioid receptor signaling.Journal of neurophysiology · 2024Article
- Chronic Morphine Induces Adaptations in Opioid Receptor Signaling in a Thalamostriatal Circuit That Are Location Dependent, Sex Specific, and Regulated by μ-Opioid Receptor Phosphorylation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Agonist-Specific Regulation of G Protein-Coupled Receptors after Chronic Opioid Treatment.Molecular pharmacology · 2022Article
- Nucleus Tractus Solitarius Neurons Activated by Hypercapnia and Hypoxia Lack Mu Opioid Receptor Expression.Frontiers in molecular neuroscience · 2022Article
- Cellular Tolerance Induced by Chronic Opioids in the Central Nervous System.Frontiers in systems neuroscience · 2022Review
- Multi-Level Regulation of Opioid-Induced Respiratory Depression.Physiology (Bethesda, Md.) · 2020Review
- Chronic Treatment with Morphine Disrupts Acute Kinase-Dependent Desensitization of GPCRs.Molecular pharmacology · 2020Article
- Recent Progress in Opioid Research from an Electrophysiological Perspective.Molecular pharmacology · 2020Review
- A cellular perspective of bias at G protein-coupled receptors.Protein science : a publication of the Protein Society · 2020Review
- Post-translational Modifications of Opioid Receptors.Trends in neurosciences · 2020Review
- Visualizing endogenous opioid receptors in living neurons using ligand-directed chemistry.eLife · 2019Article
- Separation of Acute Desensitization and Long-Term Tolerance ofMolecular pharmacology · 2019Article
- Genetic behavioral screen identifies an orphan anti-opioid system.Science (New York, N.Y.) · 2019Article
- Oxycodone-induced tolerance to respiratory depression: reversal by ethanol, pregabalin and protein kinase C inhibition.British journal of pharmacology · 2018Article
- Article
- Desensitization and Tolerance of Mu Opioid Receptors on Pontine Kölliker-Fuse Neurons.Molecular pharmacology · 2018Article
- Spinal or supraspinal phosphorylation deficiency at the MOR C-terminus does not affect morphine tolerance in vivo.Pharmacological research · 2017Article
- Effect of Tamoxifen and Brain-Penetrant Protein Kinase C and c-Jun N-Terminal Kinase Inhibitors on Tolerance to Opioid-Induced Respiratory Depression in Mice.The Journal of pharmacology and experimental therapeutics · 2017Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
μ-Opioid receptor desensitization is considered an initial step in the development of tolerance. Curiously, the commonly used opioid morphine produces robust tolerance but minimal acute desensitization. This study was designed to test the hypothesis that desensitization is indeed present in morphine-treated animals and is distinguished from cellular tolerance by time course of recovery and mechanism. To induce tolerance, rats were treated with continuously released morphine for 1 week. Morphine-mediated activation of G protein-coupled inwardly rectifying potassium conductance was measured using voltage-clamp recordings from locus ceruleus neurons in brain slices from naive or morphine-treated rats. Cellular tolerance was observed as a decrease in morphine efficacy in slices from morphine-treated rats. This tolerance persisted for at least 6 h. An additional reduction in morphine-mediated current was observed when slices from morphine-treated rats were continuously maintained in morphine at approximately the circulating plasma concentration. This additional reduction recovered within 1 h after removal of morphine from the slice and represents desensitization that developed in the tolerant animal. Recovery from desensitization, but not long-lasting tolerance, was facilitated by protein phosphatase 1 (PP1) activity. Furthermore, desensitization, but not tolerance, was reversed by protein kinase C (PKC) inhibitor but not by an inhibitor of c-Jun N-terminal kinase. Therefore, morphine treatment leads to both long-lasting cellular tolerance and readily reversible desensitization, which are differentially dependent on PP1 and PKC activity and combine to result in a substantial decrease in morphine effectiveness. This PKC-mediated desensitization may contribute to the previously reported PKC-dependent reversal of behavioral tolerance.
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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.