ArticleMolecular pharmacology2013
Ethanol reversal of cellular tolerance to morphine in rat locus coeruleus neurons.
Article in Molecular pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 15 citations in OpenAlex.
- Role of Acetaldehyde in Ethanol Reversal of Tolerance to Morphine-Induced Respiratory Depression in Mice.Advances in drug and alcohol research · 2022Article
- Oxycodone-induced tolerance to respiratory depression: reversal by ethanol, pregabalin and protein kinase C inhibition.British journal of pharmacology · 2018Article
- Ethanol Reversal of Oxycodone Tolerance in Dorsal Root Ganglia Neurons.Molecular pharmacology · 2018Article
- Reversal of oxycodone and hydrocodone tolerance by diazepam.Brain research · 2017Article
- Ethanol Reversal of Tolerance to the Antinociceptive Effects of Oxycodone and Hydrocodone.The Journal of pharmacology and experimental therapeutics · 2017Article
- Metformin reduces morphine tolerance by inhibiting microglial-mediated neuroinflammation.Journal of neuroinflammation · 2016Article
- Ethanol Reversal of Tolerance to the Respiratory Depressant Effects of Morphine.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Article
- The μ-opioid receptor: an electrophysiologist's perspective from the sharp end.British journal of pharmacology · 2015Review
- Contribution of adenylyl cyclase modulation of pre- and postsynaptic GABA neurotransmission to morphine antinociception and tolerance.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2014Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Consumption of ethanol is a considerable risk factor for death in heroin overdose. We sought to determine whether a mildly intoxicating concentration of ethanol could alter morphine tolerance at the cellular level. In rat locus coeruleus (LC) neurons, tolerance to morphine was reversed by acute exposure of the brain slice to ethanol (20 mM). Tolerance to the opioid peptide [d-Ala(2),N-MePhe(4),Gly-ol]-enkephalin was not reversed by ethanol. Previous studies in LC neurons have revealed a role for protein kinase C (PKC)α in μ-opioid receptor (MOPr) desensitization by morphine and in the induction and maintenance of morphine tolerance, but we have been unable to demonstrate that 20 mM ethanol produces significant inhibition of PKCα. The ability of ethanol to reverse cellular tolerance to morphine in LC neurons was absent in the presence of the phosphatase inhibitor okadaic acid, indicating that dephosphorylation is involved. In human embryonic kidney 293 cells expressing the MOPr, ethanol reduced the level of MOPr phosphorylation induced by morphine. Ethanol reversal of tolerance did not appear to result from a direct effect on MOPr since acute exposure to ethanol (20 mM) did not modify the affinity of binding of morphine to the MOPr or the efficacy of morphine for G-protein activation as measured by guanosine 5'-O-(3-[(35)S]thio)triphosphate binding. Similarly, ethanol did not affect MOPr trafficking. We conclude that acute exposure to ethanol enhances the effects of morphine by reversing the processes underlying morphine cellular tolerance.
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Registered trials
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.