Evidence map›Paper›PMID 28990593›Full record

ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2018

Riluzole Impairs Cocaine Reinstatement and Restores Adaptations in Intrinsic Excitability and GLT-1 Expression.

Marian T Sepulveda-Orengo, Kati L Healey, Ronald Kim, Alyson C Auriemma, Jennifer Rojas, Nicholas Woronoff, Rachel Hyppolite, Kathryn J Reissner

Open access · bronzeAbstract read
In one paragraph

Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.8field-weighted citation impact, top 16% 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

24 citing papers in PubMed, 47 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. A sex-dependent role for the prelimbic cortex in impulsive action both before and following early cocaine abstinence.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021
    Article
  15. MC-100093, a NovelThe Journal of pharmacology and experimental therapeutics · 2021
    Article
  16. Impact of Acute and Persistent Excitation of Prelimbic Pyramidal Neurons on Motor Activity and Trace Fear Learning.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021
    Article
  17. Review
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Marian T Sepulveda-OrengoDepartment of Psychology and Neuroscience, University of North Carolina, Chapel Hill, NC, USA.
Kati L HealeyDepartment of Psychology and Neuroscience, University of North Carolina, Chapel Hill, NC, USA.
Ronald KimDepartment of Psychology and Neuroscience, University of North Carolina, Chapel Hill, NC, USA.
Alyson C AuriemmaDepartment of Psychology and Neuroscience, University of North Carolina, Chapel Hill, NC, USA.
Jennifer RojasDepartment of Psychology and Neuroscience, University of North Carolina, Chapel Hill, NC, USA.ORCID 0000-0001-9553-9938
Nicholas WoronoffDepartment of Psychology and Neuroscience, University of North Carolina, Chapel Hill, NC, USA.
Rachel HyppoliteDepartment of Psychology and Neuroscience, University of North Carolina, Chapel Hill, NC, USA.
Kathryn J ReissnerDepartment of Psychology and Neuroscience, University of North Carolina, Chapel Hill, NC, USA.
University of North Carolina at Chapel Hill · US

Funding

Training on Research in Drug AbuseT32DA007244 · NIDA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Regina M Carelli · 1990 to 2026
$7.6M
Astrocyte-mediated mechanisms of cocaine seekingR01DA041455 · NIDA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI REISSNER, KATHRYN JOANNA · 2016 to 2020
$1.7M
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
NIDA NIH HHS R00 DA031790NIDA NIH HHS R01 DA041455NIDA NIH HHS T32 DA007244
6 · The paper itself

Abstract

Adaptations in glutamate signaling within the brain's reward circuitry are observed following withdrawal from several abused drugs, including cocaine. These include changes in intrinsic cellular excitability, glutamate release, and glutamate uptake. Pharmacological or optogenetic reversal of these adaptations have been shown to reduce measures of cocaine craving and seeking, raising the hypothesis that regulation of glutamatergic signaling represents a viable target for the treatment of substance use disorders. Here, we tested the hypothesis that administration of the compound riluzole, which regulates glutamate dynamics in several ways, would reduce cocaine seeking in the rat self-administration and reinstatement model of addiction. Riluzole dose-dependently inhibited cue- and cocaine-primed reinstatement to cocaine, but did not affect locomotor activity or reinstatement to sucrose seeking. Moreover, riluzole reversed bidirectional cocaine-induced adaptations in intrinsic excitability of prelimbic (PL) and infralimbic (IL) pyramidal neurons; a cocaine-induced increase in PL excitability was decreased by riluzole, and a cocaine-induced decrease in IL excitability was increased to normal levels. Riluzole also reversed the cocaine-induced suppression of the high-affinity glutamate transporter 1 (EAAT2/GLT-1) in the nucleus accumbens (NAc). GLT-1 is responsible for the majority of glutamate uptake in the brain, and has been previously reported to be downregulated by cocaine. These results demonstrate that riluzole impairs cocaine reinstatement while rectifying several cellular adaptations in glutamatergic signaling within the brain's reward circuitry, and support the hypothesis that regulators of glutamate homeostasis represent viable candidates for pharmacotherapeutic treatment of psychostimulant relapse.

Indexed as

AnimalsBrainCocaineCocaine-Related DisordersDietary SucroseDopamine Uptake InhibitorsDrug-Seeking BehaviorExcitatory Amino Acid AntagonistsExcitatory Amino Acid Transporter 2Feeding BehaviorGene Expression RegulationMaleMembrane PotentialsMotor ActivityPyramidal CellsRats, Sprague-DawleyCocaineDietary SucroseDopamine Uptake InhibitorsExcitatory Amino Acid AntagonistsExcitatory Amino Acid Transporter 2RiluzoleSlc1a2 protein, rat

Identifiers

PMID28990593
PMCPMC5916346
OpenAlexW2761575587

What OpenQuestion holds

Textmetadata
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.