Evidence map›Paper›PMID 26946381›Full record

ArticleBiological psychiatry2016

Cocaine Self-Administration and Extinction Leads to Reduced Glial Fibrillary Acidic Protein Expression and Morphometric Features of Astrocytes in the Nucleus Accumbens Core.

Michael D Scofield, Hao Li, Benjamin M Siemsen, Kati L Healey, Phuong K Tran, Nicholas Woronoff, Heather A Boger, Peter W Kalivas, Kathryn J Reissner

Abstract read
In one paragraph

Article in Biological psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers.

0numbers the graph read from it
0cells of the map it votes in
127citing papers in PubMed
9.1field-weighted citation impact, top 1% 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

127 citing papers in PubMed, 177 citations in OpenAlex.

  1. Synaptic plasticity in cocaine-seeking ensembles of the nucleus accumbens core.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Article
  2. Article
  3. The neuroimmune-glutamate hypothesis of addiction.Neuroscience and biobehavioral reviews · 2026
    Review
  4. Astrocyte TrkB.T1 Deficiency Disrupts Glutamatergic Synaptogenesis and Astrocyte-Synapse Interactions.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026
    Article
  5. Article
  6. MAO-B status in alcohol use disorder: a [Molecular psychiatry · 2026
    Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Michael D ScofieldDepartment of Neurosciences, Medical University of South Carolina, Charleston, South Carolina.
Hao LiDepartment of Neurosciences, Medical University of South Carolina, Charleston, South Carolina.
Benjamin M SiemsenDepartment of Neurosciences, Medical University of South Carolina, Charleston, South Carolina.
Kati L HealeyDepartment of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Phuong K TranDepartment of Neurosciences, Medical University of South Carolina, Charleston, South Carolina.
Nicholas WoronoffDepartment of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Heather A BogerDepartment of Neurosciences, Medical University of South Carolina, Charleston, South Carolina.
Peter W KalivasDepartment 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; Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Electronic address: reissner@unc.edu.
Medical University of South Carolina · USUniversity of North Carolina at Chapel Hill · US

Funding

Selective Restoration of KCNQ Channel Inhibition in the PFC to Inhibit Cue-InducP50DA015369 · NIDA · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI KALIVAS, PETER W · 2003 to 2017
$18.6M
Training on Research in Drug AbuseT32DA007244 · NIDA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Regina M Carelli · 1990 to 2026
$7.6M
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
Contributions of Glial Glutamate Transport and Transmission to Drug AbuseR00DA031790 · NIDA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI REISSNER, KATHRYN JOANNA · 2013 to 2016
$924k
Contributions of Nitrergic Interneurons and NO Signaling in Cocaine RelapseK99DA040004 · NIDA · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI SCOFIELD, MICHAEL DAVID · 2015 to 2016
$297k
NIDA NIH HHS K99 DA040004NIDA NIH HHS P50 DA015369NIDA NIH HHS R00 DA031790NIDA NIH HHS R01 DA003906NIDA NIH HHS R01 DA012513NIDA NIH HHS R37 DA003906NIDA NIH HHS T32 DA007244
6 · The paper itself

Abstract

backgroundAs a more detailed picture of nervous system function emerges, diversity of astrocyte function becomes more widely appreciated. While it has been shown that cocaine experience impairs astroglial glutamate uptake and release in the nucleus accumbens (NAc), few studies have explored effects of self-administration on the structure and physiology of astrocytes. We investigated the effects of extinction from daily cocaine self-administration on astrocyte characteristics including glial fibrillary acidic protein (GFAP) expression, surface area, volume, and colocalization with a synaptic marker.

methodsCocaine or saline self-administration and extinction were paired with GFAP Westerns, immunohistochemistry, and fluorescent imaging of NAc core astrocytes (30 saline-administering and 36 cocaine-administering male Sprague Dawley rats were employed). Imaging was performed using a membrane-tagged lymphocyte protein tyrosine kinase-green fluorescent protein (Lck-GFP) driven by the GFAP promoter, coupled with synapsin I immunohistochemistry.

resultsGFAP expression was significantly reduced in the NAc core following cocaine self-administration and extinction. Similarly, we observed an overall smaller surface area and volume of astrocytes, as well as reduced colocalization with synapsin I, in cocaine-administering animals. Cocaine-mediated reductions in synaptic contact were reversed by the β-lactam antibiotic ceftriaxone.

conclusionsMultiple lines of investigation indicate that NAc core astrocytes exist in a hyporeactive state following cocaine self-administration and extinction. Decreased association with synaptic elements may be particularly meaningful, as cessation of chronic cocaine use is associated with changes in synaptic strength and resistance to the induction of synaptic plasticity. We hypothesize that the reduced synaptic colocalization of astrocytes represents an important maladaptive cellular response to cocaine and the mechanisms underlying relapse vulnerability.

Indexed as

Extinction, PsychologicalAnimalsAnimals, Genetically ModifiedAstrocytesCeftriaxoneCell CountCocaineGlial Fibrillary Acidic ProteinMaleNucleus AccumbensRatsRats, Sprague-DawleySelf AdministrationSynapsesSynapsinsCeftriaxoneCocaineGlial Fibrillary Acidic ProteinSynapsinsAstrocyteCocaineColocalizationGFAPNucleus accumbensSelf-administration

Identifiers

PMID26946381
PMCPMC4930433
OpenAlexW2284615312

What OpenQuestion holds

Textmetadata
LicenceTDM
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.