Evidence map›Paper›PMID 21562274›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011

Cellular morphine tolerance produced by βarrestin-2-dependent impairment of μ-opioid receptor resensitization.

Vu C Dang, Billy Chieng, Yael Azriel, MacDonald J Christie

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
4.4field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

43 citing papers in PubMed, 68 citations in OpenAlex.

  1. Role of β-Arrestin 2 in the antinociceptive and side effect profile of morphine and the novel mu opioid receptor agonists, kurkinorin and kurkinol.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025
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  4. The Downregulation of Opioid Receptors and Neuropathic Pain.International journal of molecular sciences · 2023
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  15. Cannabinoid CBCannabis and cannabinoid research · 2017
    Review
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  18. Receptor Reserve Moderates Mesolimbic Responses to Opioids in a Humanized Mouse Model of the OPRM1 A118G Polymorphism.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2015
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 2 countries.

Vu C DangPain Management Research Institute and Kolling Institute and Brain and Mind Research Institute, The University of Sydney, Sydney, New South Wales 2006, Australia.
Billy Chieng
Yael Azriel
MacDonald J Christie
University of Sydney · AUManagement Research Institute · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chronic morphine treatment produces behavioral and cellular opioid tolerance that has been proposed to be caused by attenuated μ-opioid receptor (MOR) recovery from desensitization (resensitization). The process of MOR resensitization is thought to require βarrestin-2 (βarr-2)-dependent trafficking of desensitized receptors to endosomal compartments, followed by recycling of resensitized receptors back to the plasma membrane. However, there is little direct evidence for this, particularly in native neurons. This study used whole-cell patch-clamp recording in locus ceruleus (LC) neurons from wild-type (w.t.) and βarr-2 knock-out (k.o.) mice to examine whether βarr-2/dynamin-dependent trafficking is required for MOR resensitization in neurons from opioid-naive and morphine-treated mice. Surprisingly, recovery of MOR from acute desensitization in LC neurons does not require βarr-2- or dynamin-dependent trafficking. To the contrary, MOR resensitization was accelerated by disruption of either βarr-2 or dynamin function. Chronic morphine treatment caused cellular MOR tolerance and concurrently impaired MOR resensitization in neurons from w.t. mice, as expected from previous studies, but neither occurred in neurons from βarr-2 k.o. mice. Moreover, the impairment of MOR resensitization caused by chronic morphine was reversed in w.t. neurons when G-protein-coupled receptor kinase-2 (GRK2) or dynamin function was disrupted. Together, these results establish that βarr-2/dynamin-dependent receptor regulation is not required for MOR resensitization in LC neurons. Furthermore, chronic morphine treatment modifies GRK2-βarr-2-dynamin-dependent MOR trafficking to impair receptor resensitization, thereby contributing to opioid tolerance in LC neurons by reducing the number of functional receptors on the surface membrane.

Indexed as

AnimalsArrestinsbeta-ArrestinsDrug ToleranceDynaminsEndocytosisMiceMice, KnockoutMorphineNarcoticsNeuronsPatch-Clamp TechniquesReceptors, Opioid, muArrestinsbeta-ArrestinsDynaminsMorphineNarcoticsReceptors, Opioid, mu

Identifiers

PMID21562274
PMCPMC6703228
OpenAlexW2061189186

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.