Evidence map›Paper›PMID 31495448›Full record

ArticleBiological psychiatry2019

Heroin Cue-Evoked Astrocytic Structural Plasticity at Nucleus Accumbens Synapses Inhibits Heroin Seeking.

Anna Kruyer, Michael D Scofield, Daniel Wood, Kathryn J Reissner, Peter W Kalivas

Open access · greenAbstract read
In one paragraph

Article in Biological psychiatry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
5.3field-weighted citation impact, top 3% 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

61 citing papers in PubMed, 92 citations in OpenAlex.

  1. Article
  2. Astrocyte TrkB.T1 Deficiency Disrupts Glutamatergic Synaptogenesis and Astrocyte-Synapse Interactions.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026
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1 more citing papers are in PubMed but not listed here.

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

5 authors at 2 institutions in 1 country.

Anna KruyerDepartment of Neurosciences, Medical University of South Carolina, Charleston, South Carolina. Electronic address: kruyer@musc.edu.
Michael D ScofieldDepartment of Neurosciences, Medical University of South Carolina, Charleston, South Carolina; Department of Anesthesia and Perioperative Medicine, Medical University of South Carolina, Charleston, South Carolina.
Daniel WoodDepartment of Neurosciences, Medical University of South Carolina, Charleston, South Carolina.
Kathryn J ReissnerDepartment of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Peter W KalivasDepartment of Neurosciences, Medical University of South Carolina, Charleston, South Carolina. Electronic address: kalivasp@musc.edu.
Medical University of South Carolina · USUniversity of North Carolina at Chapel Hill · US

Funding

DRUG ABUSE TRAINING PROGRAMT32DA007288 · NIDA · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI Christopher W Cowan, Rachel Penrod-Martin · 1991 to 2026
$11.8M
COCA: Project 4. Neurocircuit Strategy to Decrease Cocaine Cue ReactivityP50DA046373 · NIDA · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI HANLON, COLLEEN A · 2019 to 2023
$9.9M
GLUTAMATE AND CRAVING FOR COCAINER01DA012513 · NIDA · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI KALIVAS, PETER W · 2000 to 2024
$7.5M
OPIOIDS, AMPHETAMINE &COCAIN IN DRUG ABUSER01DA003906 · NIDA · WASHINGTON STATE UNIVERSITY · PI KALIVAS, PETER W · 1985 to 2019
$3.6M
COCAINE, OPIOIDS AND DRUG ABUSER37DA003906 · NIDA · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI KALIVAS, PETER W · 2000 to 2009
$3.0M
Astrocyte-mediated mechanisms of cocaine seekingR01DA041455 · NIDA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI REISSNER, KATHRYN JOANNA · 2016 to 2020
$1.7M
Contributions of Nitrergic Interneurons and NO Signaling in Cocaine RelapseR00DA040004 · NIDA · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI SCOFIELD, MICHAEL DAVID · 2017 to 2019
$747k
Contributions of Nitrergic Interneurons and NO Signaling in Cocaine RelapseK99DA040004 · NIDA · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI SCOFIELD, MICHAEL DAVID · 2015 to 2016
$297k
Exploring the Mechanisms that Regulate Glutamate Overflow in Addiction and RelapseF32DA044782 · NIDA · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI KRUYER, ANNA K · 2018 to 2018
$47k
NIDA NIH HHS F32 DA044782NIDA NIH HHS K99 DA040004NIDA NIH HHS P50 DA046373NIDA NIH HHS R00 DA040004NIDA NIH HHS R01 DA003906NIDA NIH HHS R01 DA012513NIDA NIH HHS R01 DA041455NIDA NIH HHS R37 DA003906NIDA NIH HHS T32 DA007288
6 · The paper itself

Abstract

backgroundOpioid addiction is a critical medical and societal problem characterized by vulnerability to relapse. Glutamatergic synapses in the nucleus accumbens regulate the motivation to relapse to opioid use, and downregulation of glutamate transporters on astroglial processes adjacent to accumbens synapses contributes to heroin seeking induced by cues. However, it is not known how astroglial processes themselves respond to heroin cues or if changes in astroglial morphology are necessary for heroin seeking.

methodsMale Sprague Dawley rats (n = 62) were trained to self-administer heroin or sucrose and were reinstated by heroin-conditioned or sucrose-conditioned cues. Astroglial proximity to accumbens synapses was estimated using a confocal-based strategy, and the association between digitally isolated astroglia and the presynaptic marker synapsin I was quantified. To determine the functional consequence of astroglial morphological plasticity on cued heroin seeking, a morpholino antisense strategy was used to knock down expression of the actin binding protein ezrin, which is expressed almost exclusively in peripheral astroglial processes in the adult rat brain.

resultsAfter heroin extinction, there was an enduring reduction in synaptic proximity by astroglia. Synaptic proximity was restored during 15 minutes of cued heroin seeking but returned to extinction levels by 120 minutes. Extinction from sucrose self-administration and reinstated sucrose seeking induced no changes in astroglial synaptic association. Ezrin knockdown reduced astroglial association with synapses and potentiated cued heroin seeking.

conclusionsCue-induced heroin seeking transiently increased synaptic proximity of accumbens astrocytes. Surprisingly, the reassociation of astroglia with synapses was compensatory, and preventing cue-induced morphological plasticity in astrocytes potentiated heroin seeking.

Indexed as

CuesAnimalsAstrocytesCytoskeletal ProteinsDrug-Seeking BehaviorExtinction, PsychologicalEzrinGene Knockdown TechniquesHeroinMaleNeuronal PlasticityNucleus AccumbensRatsRats, Sprague-DawleySelf AdministrationSynapsesCytoskeletal ProteinsEzrinHeroinAddictionAstrocyteHeroinNucleus accumbensSelf-administrationSynapse

Identifiers

PMID31495448
PMCPMC6823145
OpenAlexW2961579768

What OpenQuestion holds

Textmetadata
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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.