Evidence map›Paper›PMID 40802516›Full record

ArticleCell reports2025

Abstinence from cocaine self-administration promotes microglial pruning of astrocytes, which drives cocaine-seeking behavior.

Anze Testen, Jonathan W VanRyzin, Tania J Bellinger, Ronald Kim, Han Wang, Matthew J Gastinger, Emily A Witt, Janay P Franklin, Haley A Vecchiarelli, Katherine Picard and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. The neuroimmune-glutamate hypothesis of addiction.Neuroscience and biobehavioral reviews · 2026
    Review
  2. Article
  3. Review
  4. Review
  5. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Anze TestenDepartment of Psychology and Neuroscience, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA; Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
Jonathan W VanRyzinDepartment of Psychology and Neuroscience, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA.
Tania J BellingerDepartment of Psychology and Neuroscience, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA.
Ronald KimSection on Genetics of Neuronal Signaling, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Han WangMS-HCI Program, Georgia Institute of Technology, Atlanta, GA, USA.
Matthew J GastingerBitplane - Oxford Instruments, Concord, MA, USA.
Emily A WittDepartment of Medical Neuroscience, Dalhousie University, Halifax, NS, Canada.
Janay P FranklinDepartment of Psychology and Neuroscience, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA.
Haley A VecchiarelliDivision of Medical Sciences, University of Victoria, Victoria, BC, Canada.
Katherine PicardDivision of Medical Sciences, University of Victoria, Victoria, BC, Canada.
Michael D ScofieldDepartment of Anesthesiology and Perioperative Medicine, Medical University of South Carolina, Charleston, SC, USA.
Marie-Ève TremblayDivision of Medical Sciences, University of Victoria, Victoria, BC, Canada; Centre for Advanced Materials and Related Technology (CAMTEC), University of Victoria, Victoria, BC, Canada; Institute for Aging and Lifelong Health (IALH), University of Victoria, Victoria, BC, Canada; Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, BC, Canada.
Kathryn J ReissnerDepartment of Psychology and Neuroscience, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA. Electronic address: kreissne@email.unc.edu.

Funding

Functional consequences of cocaine self-administration on astrocytesR01DA057776 · NIDA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Kathryn Joanna Reissner · 2023 to 2026
$1.4M
NIDA NIH HHS R01 DA057776
6 · The paper itself

Abstract

Rodent drug self-administration leads to a compromised ability of nucleus accumbens astrocytes to maintain glutamate homeostasis as well as to reductions in surface area, volume, and synaptic colocalization of astrocyte membranes. However, the mechanisms driving astrocyte responses to drug administration are unknown. Here, we report that long-access rat cocaine self-administration followed by prolonged home cage abstinence results in decreased branching complexity of nucleus accumbens astrocytes, characterized by the loss of peripheral processes. Using a combination of confocal fluorescence microscopy and immunoelectron microscopy, we show that these alterations in astrocyte structural features are driven by microglial phagocytosis, as virally labeled astrocyte membranes are found within microglial phagolysosomes. Inhibition of complement C3-mediated phagocytosis using the neutrophil inhibitory peptide (NIF) rescued astrocyte structure and decreased cocaine-seeking behavior following cocaine self-administration and abstinence. Collectively, these results provide evidence for microglial pruning of nucleus accumbens astrocytes across cocaine abstinence, which mediates cocaine craving.

Indexed as

AstrocytesCocaineCocaine-Related DisordersDrug-Seeking BehaviorMicrogliaAnimalsMaleNucleus AccumbensPhagocytosisRatsRats, Sprague-DawleySelf AdministrationCocaineastrocytescocaineCP: Neurosciencedrug seekingmicroglianucleus accumbensphagocytosisrelapse

Identifiers

PMID40802516
PMCPMC12788899

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.