Evidence map›Paper›PMID 25199705›Full record

ArticleNeuron2014

Bidirectional modulation of incubation of cocaine craving by silent synapse-based remodeling of prefrontal cortex to accumbens projections.

Yao-Ying Ma, Brian R Lee, Xiusong Wang, Changyong Guo, Lei Liu, Ranji Cui, Yan Lan, Judith J Balcita-Pedicino, Marina E Wolf, Susan R Sesack and 4 more

Erratum issuedAbstract read
In one paragraph

Article in Neuron, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 254 papers.

0numbers the graph read from it
0cells of the map it votes in
254citing papers in PubMed
–field-weighted citation impact
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

254 citing papers in PubMed.

  1. Contrasting roles of secondary motor cortex projections to the dorsolateral and dorsomedial striatum in incubation of cocaine-seeking.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Article
  2. The neuroimmune-glutamate hypothesis of addiction.Neuroscience and biobehavioral reviews · 2026
    Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Acetazolamide inhibition of carbonic anhydrase 4 reverses opioid-induced synaptic rearrangements in nucleus accumbens and reduces drug-seeking behavior.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. The role of the prelimbic cortex to nucleus accumbens core projection in the reinstatement of cocaine-seeking after cocaine-alcohol polysubstance use.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Article
  13. Article
  14. Sense of agency and addiction.Frontiers in psychology · 2026
    Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article

194 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Yao-Ying MaDepartment of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Brian R LeeAllen Institute for Brain Science, Seattle, WA 98103, USA.
Xiusong WangDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Changyong GuoDepartment of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Lei LiuSchool of Life Science, Northeastern Normal University, Jilin, China.
Ranji CuiSchool of Life Science, Northeastern Normal University, Jilin, China.
Yan LanDepartment of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Judith J Balcita-PedicinoDepartment of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Marina E WolfDepartment of Neuroscience, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA.
Susan R SesackDepartment of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA; Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Yavin ShahamBehavioral Neuroscience Branch, Intramural Research Program, NIDA, NIH, Baltimore, MD 21224, USA.
Oliver M SchlüterMolecular Neurobiology and Cluster of Excellence "Nanoscale Microscopy and Molecular Physiology of the Brain," European Neuroscience Institute, 37077 Göttingen, Germany.
Yanhua H HuangDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15260, USA. Electronic address: huangy3@upmc.edu.
Yan DongDepartment of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA; Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15260, USA. Electronic address: yandong@pitt.edu.

Funding

Neurobiology Of Relapse To Opiate and Psychostimulant DrugsZIADA000434 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI SHAHAM, YAVIN · 2009 to 2025
$39.8M
Reversal of AMPA receptor plasticity underlying incubation of cocaine cravingR01DA009621 · NIDA · ROSALIND FRANKLIN UNIV OF MEDICINE &SCI · PI Marina Elizabeth Wolf · 1996 to 2026
$8.5M
Cocaine-induced adaptation in NMDA receptorsR37DA023206 · NIDA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Yan Dong · 2018 to 2026
$3.9M
Cocaine-induced Adaptation in NMDA Receptors in Nucleus AccumbensR01DA023206 · NIDA · WASHINGTON STATE UNIVERSITY · PI DONG, YAN · 2008 to 2017
$3.0M
Dopamine and Glutamate Receptor InteractionsR37DA015835 · NIDA · ROSALIND FRANKLIN UNIV OF MEDICINE &SCI · PI WOLF, MARINA ELIZABETH · 2003 to 2012
$2.8M
Dopamine Signaling and Synaptic Plasticity in the Nucleus AccumbensR01MH101147 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI HUANG, YANHUA H · 2014 to 2018
$1.9M
Synaptic mechanisms maintaining persistent cocaine craving.R01DA015835 · NIDA · ROSALIND FRANKLIN UNIV OF MEDICINE & SCI · PI WOLF, MARINA ELIZABETH · 2014 to 2018
$1.8M
Synaptic Reorganization in Drug AddictionR01DA035805 · NIDA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI HUANG, YANHUA H · 2014 to 2018
$1.7M
Homeostatic Regulation and Dysregulation in Cocaine CravingR01DA034856 · NIDA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DONG, YAN · 2013 to 2017
$1.5M
Homeostatic Plasticity in Nucleus AccumbensR01DA030379 · NIDA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DONG, YAN, MALENKA, ROBERT C · 2013 to 2014
$880k
Regulation of Nucleus Accumbens Neurons by Sleep DeprivationR00DA029565 · NIDA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI HUANG, YANHUA H · 2012 to 2014
$728k
Regulation of Nucleus Accumbens Neurons by Sleep DeprivationK99DA029565 · NIDA · WASHINGTON STATE UNIVERSITY · PI HUANG, YANHUA H · 2011 to 2012
$244k
Intramural NIH HHSNIDA NIH HHS DA009621NIDA NIH HHS DA015835NIDA NIH HHS DA023206NIDA NIH HHS DA028020NIDA NIH HHS DA029565NIDA NIH HHS DA030379NIDA NIH HHS DA034856NIDA NIH HHS DA035805NIDA NIH HHS F31 DA028020NIDA NIH HHS K99 DA029565NIDA NIH HHS R00 DA029565NIDA NIH HHS R01 DA009621NIDA NIH HHS R01 DA015835NIDA NIH HHS R01 DA023206NIDA NIH HHS R01 DA030379NIDA NIH HHS R01 DA034856NIDA NIH HHS R01 DA035805NIDA NIH HHS R37 DA015835NIDA NIH HHS R37 DA023206NIMH NIH HHS MH101147NIMH NIH HHS R01 MH101147
6 · The paper itself

Abstract

Glutamatergic projections from the medial prefrontal cortex (mPFC) to nucleus accumbens (NAc) contribute to cocaine relapse. Here we show that silent synapse-based remodeling of the two major mPFC-to-NAc projections differentially regulated the progressive increase in cue-induced cocaine seeking after withdrawal (incubation of cocaine craving). Specifically, cocaine self-administration in rats generated AMPA receptor-silent glutamatergic synapses within both infralimbic (IL) and prelimbic mPFC (PrL) to NAc projections, measured after 1 day of withdrawal. After 45 days of withdrawal, IL-to-NAc silent synapses became unsilenced/matured by recruiting calcium-permeable (CP) AMPARs, whereas PrL-to-NAc silent synapses matured by recruiting non-CP-AMPARs, resulting in differential remodeling of these projections. Optogenetic reversal of silent synapse-based remodeling of IL-to-NAc and PrL-to-NAc projections potentiated and inhibited, respectively, incubation of cocaine craving on withdrawal day 45. Thus, pro- and antirelapse circuitry remodeling is induced in parallel after cocaine self-administration. These results may provide substrates for utilizing endogenous antirelapse mechanisms to reduce cocaine relapse.

Indexed as

AnimalsCocaine-Related DisordersCravingDrug-Seeking BehaviorElectrophysiologyMaleNeural PathwaysNeuronal PlasticityNucleus AccumbensOptogeneticsPrefrontal CortexRatsRats, Sprague-DawleySynapses

Identifiers

PMID25199705
PMCPMC4295617

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Registered trials

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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.