Evidence map›Paper›PMID 26769453›Full record

ArticleAddiction biology2017

Cocaine craving during protracted withdrawal requires PKCε priming within vmPFC.

Bailey W Miller, Melissa G Wroten, Arianne D Sacramento, Hannah E Silva, Christina B Shin, Philip A Vieira, Osnat Ben-Shahar, Tod E Kippin, Karen K Szumlinski

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

Article in Addiction biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.7field-weighted citation impact, top 19% 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

23 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Inactivation of NMDAR and CaMKII signaling within the prelimbic cortex blocks incubated cocaine- and sucrose-craving.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Preclinical evidence to support repurposing everolimus for craving reduction during protracted drug withdrawal.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021
    Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. Modeling the development of drug addiction in male and female animals.Pharmacology, biochemistry, and behavior · 2018
    Review
  20. Article
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

9 authors at 1 institution in 1 country.

Bailey W MillerDepartment of Psychological and Brain Sciences and Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA, USA.
Melissa G WrotenDepartment of Psychological and Brain Sciences and Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA, USA.
Arianne D SacramentoDepartment of Psychological and Brain Sciences and Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA, USA.
Hannah E SilvaDepartment of Psychological and Brain Sciences and Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA, USA.
Christina B ShinDepartment of Psychological and Brain Sciences and Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA, USA.
Philip A VieiraDepartment of Psychological and Brain Sciences and Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA, USA.
Osnat Ben-ShaharDepartment of Psychological and Brain Sciences and Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA, USA.
Tod E KippinDepartment of Psychological and Brain Sciences and Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA, USA.
Karen K SzumlinskiDepartment of Psychological and Brain Sciences and Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA, USA.
University of California, Santa Barbara · US

Funding

Interactions between prenatal stress and genetics in cocaine responsiveness.R01DA027525 · NIDA · UNIVERSITY OF CALIFORNIA SANTA BARBARA · PI KIPPIN, TOD EDWARD · 2010 to 2014
$1.6M
Homer-mediated signaling and cocaine addictionR01DA024038 · NIDA · UNIVERSITY OF CALIFORNIA SANTA BARBARA · PI SZUMLINSKI, KAREN KATHLEEN · 2008 to 2012
$1.5M
NIDA NIH HHS R01 DA024038NIDA NIH HHS R01 DA027525
6 · The paper itself

Abstract

In individuals with a history of drug taking, the capacity of drug-associated cues to elicit indices of drug craving intensifies or incubates with the passage of time during drug abstinence. This incubation of cocaine craving, as well as difficulties with learning to suppress drug-seeking behavior during protracted withdrawal, are associated with a time-dependent deregulation of ventromedial prefrontal cortex (vmPFC) function. As the molecular bases for cocaine-related vmPFC deregulation remain elusive, the present study assayed the consequences of extended access to intravenous cocaine (6 hours/day; 0.25 mg/infusion for 10 day) on the activational state of protein kinase C epsilon (PKCε), an enzyme highly implicated in drug-induced neuroplasticity. The opportunity to engage in cocaine seeking during cocaine abstinence time-dependently altered PKCε phosphorylation within vmPFC, with reduced and increased p-PKCε expression observed in early (3 days) and protracted (30 days) withdrawal, respectively. This effect was more robust within the ventromedial versus dorsomedial PFC, was not observed in comparable cocaine-experienced rats not tested for drug-seeking behavior and was distinct from the rise in phosphorylated extracellular signal-regulated kinase observed in cocaine-seeking rats. Further, the impact of inhibiting PKCε translocation within the vmPFC using TAT infusion proteins upon cue-elicited responding was determined and inhibition coinciding with the period of testing attenuated cocaine-seeking behavior, with an effect also apparent the next day. In contrast, inhibitor pretreatment prior to testing during early withdrawal was without effect. Thus, a history of excessive cocaine taking influences the cue reactivity of important intracellular signaling molecules within the vmPFC, with PKCε playing a critical role in the manifestation of cue-elicited cocaine seeking during protracted drug withdrawal.

Indexed as

AnimalsBehavior, AnimalCocaineCocaine-Related DisordersCravingDisease Models, AnimalDopamine Uptake InhibitorsDrug-Seeking BehaviorImmunoblottingMalePrefrontal CortexProtein Kinase C-epsilonRatsRats, Sprague-DawleySubstance Withdrawal SyndromeCocaineDopamine Uptake InhibitorsProtein Kinase C-epsilonCocainecravingERKincubationPKC epsilonprefrontal cortex

Identifiers

PMID26769453
PMCPMC4945488
OpenAlexW2235910195

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.