Evidence map›Paper›PMID 34742997›Full record

ArticleBrain stimulation

Deep brain stimulation of the nucleus accumbens shell attenuates cocaine withdrawal but increases cocaine self-administration, cocaine-induced locomotor activity, and GluR1/GluA1 in the central nucleus of the amygdala in male cocaine-dependent rats.

Marsida Kallupi, Jenni Kononoff, Philippe A Melas, Johanna S Qvist, Giordano de Guglielmo, Eric R Kandel, Olivier George

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Brain stimulation. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 4 pooled it
2.0field-weighted citation impact, top 11% 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

16 citing papers in PubMed, 4 syntheses or guidelines pooled it, 20 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
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  4. Pooled it
  5. Article
  6. Review
  7. Article
  8. Article
  9. Deep brain stimulation for psychostimulant use disorders.Journal of neural transmission (Vienna, Austria : 1996) · 2024
    Review
  10. Article
  11. Article
  12. High frequency DBS-like optogenetic stimulation of nucleus accumbens dopamine D2 receptor-containing neurons attenuates cocaine reinstatement in male rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023
    Article
  13. Review
  14. Role of deep brain stimulation (DBS) in addiction disorders.Surgical neurology international · 2023
    Review
  15. Article
  16. 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

7 authors at 4 institutions in 2 countries.

Marsida KallupiDepartment of Psychiatry, University of California, San Diego School of Medicine, San Diego, CA, 92093, USA; Department of Neuroscience, The Scripps Research Institute, 10550 N.Torrey Pines Rd, La Jolla, CA, 92037, USA. Electronic address: mkallupi@health.ucsd.edu.
Jenni KononoffDepartment of Neuroscience, The Scripps Research Institute, 10550 N.Torrey Pines Rd, La Jolla, CA, 92037, USA.
Philippe A MelasDepartment of Neuroscience, Columbia University, New York, NY, 10032, USA; Mortimer B. Zuckerman Mind Brain Behavior Institute, Jerome L. Greene Science Center, New York, NY, 10027, USA; Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, 17176, Sweden.
Johanna S QvistDepartment of Neuroscience, Columbia University, New York, NY, 10032, USA; Mortimer B. Zuckerman Mind Brain Behavior Institute, Jerome L. Greene Science Center, New York, NY, 10027, USA.
Giordano de GuglielmoDepartment of Psychiatry, University of California, San Diego School of Medicine, San Diego, CA, 92093, USA; Department of Neuroscience, The Scripps Research Institute, 10550 N.Torrey Pines Rd, La Jolla, CA, 92037, USA.
Eric R KandelDepartment of Neuroscience, Columbia University, New York, NY, 10032, USA; Mortimer B. Zuckerman Mind Brain Behavior Institute, Jerome L. Greene Science Center, New York, NY, 10027, USA; Kavli Institute for Brain Science, Columbia University, New York, NY, 10032, USA; Howard Hughes Medical Institute, Chevy Chase, MD, 20815, USA.
Olivier GeorgeDepartment of Psychiatry, University of California, San Diego School of Medicine, San Diego, CA, 92093, USA; Department of Neuroscience, The Scripps Research Institute, 10550 N.Torrey Pines Rd, La Jolla, CA, 92037, USA. Electronic address: olgeorge@health.ucsd.edu.
Scripps Research Institute · USColumbia University · USHoward Hughes Medical Institute · USKarolinska University Hospital · SE

Funding

Identification of Genetic Variants that Contribute to Compulsive Cocaine Intakein RatsU01DA043799 · NIDA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Olivier George, Abraham A Palmer · 2017 to 2026
$7.9M
A Novel Pharmacotherapy for Alcoholism: Evaluation of Reward, Aversion, Compulsivity, Withdrawal & ReinstatementR01AA026281 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PALMER, ABRAHAM A · 2018 to 2022
$2.0M
NIAAA NIH HHS R01 AA026281NIDA NIH HHS U01 DA043799
6 · The paper itself

Abstract

backgroundCocaine addiction is a major public health problem. Despite decades of intense research, no effective treatments are available. Both preclinical and clinical studies strongly suggest that deep brain stimulation of the nucleus accumbens (NAcc) is a viable target for the treatment of cocaine use disorder (CUD).

objectiveAlthough previous studies have shown that DBS of the NAcc decreases cocaine seeking and reinstatement, the effects of DBS on cocaine intake in cocaine-dependent animals have not yet been investigated.

methodsRats were made cocaine dependent by allowing them to self-administer cocaine in extended access conditions (6 h/day, 0.5 mg/kg/infusion). The effects of monophasic bilateral high-frequency DBS (60 μs pulse width and 130 Hz frequency) stimulation with a constant current of 150 μA of the NAcc shell on cocaine intake was then evaluated. Furthermore, cocaine-induced locomotor activity, irritability-like behavior during cocaine abstinence, and the levels of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits 1 and 2 (GluR1/GluA1 and GluR2/GluA2) after DBS were investigated.

resultsContrary to our expectations, DBS of the NAcc shell induced a slight increase in cocaine self-administration, and increased cocaine-induced locomotion after extended access of cocaine self-administration. In addition, DBS decreased irritability-like behavior 18 h into cocaine withdrawal. Finally, DBS increased both cytosolic and synaptosomal levels of GluR1, but not GluR2, in the central nucleus of the amygdala but not in other brain regions.

conclusionsThese preclinical results with cocaine-dependent animals support the use of high-frequency DBS of the NAcc shell as a therapeutic approach for the treatment of the negative emotional state that emerges during cocaine abstinence, but also demonstrate that DBS does not decrease cocaine intake in active, long-term cocaine users. These data, together with the existing evidence that DBS of the NAcc shell reduces the reinstatement of cocaine seeking in abstinent animals, suggest that NAcc shell DBS may be beneficial for the treatment of the negative emotional states and craving during abstinence, although it may worsen cocaine use if individuals continue drug use.

Indexed as

Central Amygdaloid NucleusCocaineCocaine-Related DisordersDeep Brain StimulationAnimalsLocomotionMaleNucleus AccumbensRatsSelf AdministrationCocaineAmygdalaCocaine addictionGlutamateHigh-frequency stimulationNeuromodulationWithdrawal

Identifiers

PMID34742997
PMCPMC8816878
OpenAlexW3208764031

What OpenQuestion holds

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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.