Evidence map›Paper›PMID 31596232›Full record

ArticleeLife2019

Cocaine-induced endocannabinoid signaling mediated by sigma-1 receptors and extracellular vesicle secretion.

Yoki Nakamura, Dilyan I Dryanovski, Yuriko Kimura, Shelley N Jackson, Amina S Woods, Yuko Yasui, Shang-Yi Tsai, Sachin Patel, Daniel P Covey, Tsung-Ping Su and 1 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

34 citing papers in PubMed, 50 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Choline-An Essential Nutrient with Health Benefits and a Signaling Molecule.International journal of molecular sciences · 2025
    Review
  6. Article
  7. Article
  8. The endocannabinoid 2-arachidonoylglycerol is released and transported on demand via extracellular microvesicles.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Sigma-1 receptor and seizures.Pharmacological research · 2023
    Review
  16. Article
  17. Review
  18. Article
  19. Review
  20. Review
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

11 authors at 2 institutions in 1 country.

Yoki Nakamura *Cellular Pathobiology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, United States.
Dilyan I Dryanovski *Electrophysiology Research Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, United States.
Yuriko KimuraCellular Pathobiology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, United States.
Shelley N JacksonStructural Biology Unit, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, United States.
Amina S WoodsStructural Biology Unit, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, United States.
Yuko YasuiCellular Pathobiology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, United States.
Shang-Yi TsaiCellular Pathobiology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, United States.
Sachin PatelCellular Pathobiology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, United States.ORCID 0000-0001-8052-520X
Daniel P CoveyDepartment of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, United States.ORCID 0000-0001-9596-108X
Tsung-Ping SuCellular Pathobiology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, United States.
Carl R LupicaElectrophysiology Research Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, United States.ORCID 0000-0002-5375-3263
National Institutes of Health · USUniversity of Maryland, Baltimore · US

Funding

Biological And Biochemical Characterization Of Sigma ReceptorsZIADA000206 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI SU, TSUNG PING · 2009 to 2025
$23.6M
Research Project: Sensory and Multisensory Contributions to AutismU54HD083211 · NICHD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI DYKENS, ELISABETH MAY · 2015 to 2019
$7.1M
Molecular sites of delta-9-THC and synthetic cannabinoid actions on brain functionZIADA000487 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI LUPICA, CARL · 2009 to 2021
$6.6M
Intramural NIH HHS ZIA DA000206Intramural NIH HHS ZIA DA000487NICHD NIH HHS U54 HD083211NIDA NIH HHS 1ZIADA000206-33NIDA NIH HHS 1ZIADA000487-14
6 · The paper itself

Abstract

Cocaine is an addictive drug that acts in brain reward areas. Recent evidence suggests that cocaine stimulates synthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG) in midbrain, increasing dopamine neuron activity via disinhibition. Although a mechanism for cocaine-stimulated 2-AG synthesis is known, our understanding of 2-AG release is limited. In NG108 cells and mouse midbrain tissue, we find that 2-AG is localized in non-synaptic extracellular vesicles (EVs) that are secreted in the presence of cocaine via interaction with the chaperone protein sigma-1 receptor (Sig-1R). The release of EVs occurs when cocaine causes dissociation of the Sig-1R from ADP-ribosylation factor (ARF6), a G-protein regulating EV trafficking, leading to activation of myosin light chain kinase (MLCK). Blockade of Sig-1R function, or inhibition of ARF6 or MLCK also prevented cocaine-induced EV release and cocaine-stimulated 2-AG-modulation of inhibitory synapses in DA neurons. Our results implicate the Sig-1R-ARF6 complex in control of EV release and demonstrate that cocaine-mediated 2-AG release can occur via EVs.

Indexed as

ADP-Ribosylation Factor 6ADP-Ribosylation FactorsAnimalsCocaineEndocannabinoidsExtracellular VesiclesMesencephalonMiceMyosin-Light-Chain KinaseReceptors, sigmaSigma-1 ReceptorSignal TransductionADP-Ribosylation Factor 6ADP-Ribosylation FactorsArf6 protein, mouseCocaineEndocannabinoidsMyosin-Light-Chain KinaseReceptors, sigmaSigma-1 ReceptorADP-ribosylation factor 6cannabinoidcell biologydopamine neuronendosomeguanine nucleotide exchange factormicrovesiclemouseneuroscience

Identifiers

PMID31596232
PMCPMC6850780
OpenAlexW2979555307

What OpenQuestion holds

Textmetadata
LicenceCC0
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.