1. Neuroscience
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Discriminative stimuli are sufficient for incubation of cocaine craving

  1. Rajtarun Madangopal
  2. Brendan J Tunstall
  3. Lauren E Komer
  4. Sophia J Weber
  5. Jennifer K Hoots
  6. Veronica A Lennon
  7. Jennifer M Bossert
  8. David H Epstein
  9. Yavin Shaham
  10. Bruce T Hope  Is a corresponding author
  1. National Institute on Drug Abuse, National Institutes of Health, United States
Research Article
  • Cited 7
  • Views 2,444
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Cite this article as: eLife 2019;8:e44427 doi: 10.7554/eLife.44427

Abstract

In abstinent drug addicts, cues formerly associated with drug-taking experiences gain relapse-inducing potency ('incubate') over time. Animal models of incubation may help develop treatments to prevent relapse, but these models have ubiquitously focused on the role of conditioned stimuli (CSs) signaling drug delivery. Discriminative stimuli (DSs) are unique in that they exert stimulus-control over both drug taking and drug seeking behavior and are difficult to extinguish. For this reason, incubation of the excitatory effects of DSs that signal drug availability, not yet examined in preclinical studies, could be relevant to relapse prevention. We trained rats to self-administer cocaine (or palatable food) under DS control, then investigated DS-controlled incubation of craving, in the absence of drug-paired CSs. DS-controlled cocaine (but not palatable food) seeking incubated over 60 days of abstinence and persisted up to 300 days. Understanding the neural mechanisms of this DS-controlled incubation holds promise for drug relapse treatments.

Data availability

All data generated or analyzed during this study, and needed to evaluate the conclusions in the paper, are included in the manuscript and supplementary materials.

Article and author information

Author details

  1. Rajtarun Madangopal

    Neuronal Ensembles in Addiction Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Brendan J Tunstall

    Neurobiology of Addiction Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Lauren E Komer

    Neuronal Ensembles in Addiction Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Sophia J Weber

    Neuronal Ensembles in Addiction Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Jennifer K Hoots

    Neurobiology of Relapse Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Veronica A Lennon

    Neuronal Ensembles in Addiction Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Jennifer M Bossert

    Neurobiology of Relapse Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. David H Epstein

    Real-world Assessment, Prediction, and Treatment Unit, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Yavin Shaham

    Neurobiology of Relapse Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Bruce T Hope

    Neuronal Ensembles in Addiction Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, United States
    For correspondence
    bhope@intra.nida.nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5804-7061

Funding

National Institute on Drug Abuse (DA000467-15)

  • Bruce T Hope

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health (8th edition; http://grants.nih.gov/grants/olaw/Guide-for-the-Care-and-Use-of-Laboratory-Animals.pdf). All rat experiments were approved by the Institutional Animal Care and Use Committee (Protocol# 17-BNRB-203) of the Intramural Research Program of the National Institute on Drug Abuse.

Reviewing Editor

  1. Kate M Wassum, University of California Los Angeles, United States

Publication history

  1. Received: December 14, 2018
  2. Accepted: February 20, 2019
  3. Accepted Manuscript published: February 25, 2019 (version 1)
  4. Version of Record published: March 14, 2019 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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