ArticlePloS one2011
Chronic ethanol consumption in rats produces opioid antinociceptive tolerance through inhibition of mu opioid receptor endocytosis.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 30 citations in OpenAlex.
- Alcohol and Opioids Modulate Excitatory Inputs to the SCN.bioRxiv : the preprint server for biology · 2026Article
- The Role of Endogenous Beta-Endorphin and Enkephalins in the Crosstalk Between Ethanol and Morphine.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Differential regulation of G protein-coupled receptor-associated proteins in the caudate and the putamen of cynomolgus macaques following chronic ethanol drinking.Journal of neurochemistry · 2024Article
- Deletion of arrestin-3 does not reduce drug-seeking behavior in a longitudinal paradigm of oral morphine self-administration.Frontiers in pharmacology · 2024Article
- Pharmacological and genetic manipulations at the µ-opioid receptor reveal arrestin-3 engagement limits analgesic tolerance and does not exacerbate respiratory depression in mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Drug addiction co-morbidity with alcohol: Neurobiological insights.International review of neurobiology · 2021Review
- Nicotine increases alcohol self-administration in male rats via a μ-opioid mechanism within the mesolimbic pathway.British journal of pharmacology · 2020Article
- Behavioral, neurobiological, and neurochemical mechanisms of ethanol self-administration: A translational review.Pharmacology & therapeutics · 2020Review
- Bi-directional Acceleration of Alcohol Use and Opioid Use Disorder.Journal of drug and alcohol research · 2019Article
- Binge-Like Exposure to Ethanol Enhances Morphine's Anti-nociception in B6 Mice.Frontiers in psychiatry · 2018Article
- The association between frequent alcohol drinking and opioid consumption after abdominal surgery: A retrospective analysis.PloS one · 2017Article
- Ethanol Reversal of Tolerance to the Respiratory Depressant Effects of Morphine.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Article
- Interrelations between pain and alcohol: An integrative review.Clinical psychology review · 2015Review
- Diabetes-causing gene, kruppel-like factor 11, modulates the antinociceptive response of chronic ethanol intake.Alcoholism, clinical and experimental research · 2014Article
- Ethanol reversal of cellular tolerance to morphine in rat locus coeruleus neurons.Molecular pharmacology · 2013Article
- 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
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It is well known that the mu-opioid receptor (MOR) plays an important role in the rewarding properties of ethanol. However, it is less clear how chronic ethanol consumption affects MOR signaling. Here, we demonstrate that rats with prolonged voluntary ethanol consumption develop antinociceptive tolerance to opioids. Signaling through the MOR is controlled at many levels, including via the process of endocytosis. Importantly, agonists at the MOR that promote receptor endocytosis, such as the endogenous peptides enkephalin and β-endorphin, show a reduced propensity to promote antinociceptive tolerance than do agonists, like morphine, which do not promote receptor endocytosis. These observations led us to examine whether chronic ethanol consumption produced opioid tolerance by interfering with MOR endocytosis. Indeed, here we show that chronic ethanol consumption inhibits the endocytosis of MOR in response to opioid peptide. This loss of endocytosis was accompanied by a dramatic decrease in G protein coupled receptor kinase 2 (GRK2) protein levels after chronic drinking, suggesting that loss of this component of the trafficking machinery could be a mechanism by which endocytosis is lost. We also found that MOR coupling to G-protein was decreased in ethanol-drinking rats, providing a functional explanation for loss of opioid antinociception. Together, these results suggest that chronic ethanol drinking alters the ability of MOR to endocytose in response to opioid peptides, and consequently, promotes tolerance to the effects of opioids.
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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.