Mesolimbic dopamine projections mediate cue-motivated reward seeking but not reward retrieval in rats

  1. Briac Halbout  Is a corresponding author
  2. Andrew T Marshall
  3. Ali Azimi
  4. Mimi Liljeholm
  5. Stephen V Mahler
  6. Kate M Wassum
  7. Sean B Ostlund  Is a corresponding author
  1. University of California, Irvine, United States
  2. University of California, Los Angeles, United States

Abstract

Efficient foraging requires an ability to coordinate discrete reward-seeking and reward-retrieval behaviors. We used pathway-specific chemogenetic inhibition to investigate how rats' mesolimbic and mesocortical dopamine circuits contribute to the expression and modulation of reward seeking and retrieval. Inhibiting ventral tegmental area dopamine neurons disrupted the tendency for reward-paired cues to motivate reward seeking, but spared their ability to increase attempts to retrieve reward. Similar effects were produced by inhibiting dopamine inputs to nucleus accumbens, but not medial prefrontal cortex. Inhibiting dopamine neurons spared the suppressive effect of reward devaluation on reward seeking, an assay of goal-directed behavior. Attempts to retrieve reward persisted after devaluation, indicating they were habitually performed as part of a fixed action sequence. Our findings show that complete bouts of reward seeking and retrieval are behaviorally and neurally dissociable from bouts of reward seeking without retrieval. This dichotomy may prove useful for uncovering mechanisms of maladaptive behavior.

Data availability

All data generated and analyzed during this study are included in supporting files. Source data files have been provided for Figures 1, 3, 4 and 5, as well as their respective supplemental figures.

Article and author information

Author details

  1. Briac Halbout

    Department of Anesthesiology and Perioperative Care, University of California, Irvine, Irvine, United States
    For correspondence
    halboutb@uci.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6128-2601
  2. Andrew T Marshall

    Department of Anesthesiology and Perioperative Care, University of California, Irvine, Irvine, United States
    Competing interests
    No competing interests declared.
  3. Ali Azimi

    Department of Anesthesiology and Perioperative Care, University of California, Irvine, Irvine, United States
    Competing interests
    No competing interests declared.
  4. Mimi Liljeholm

    Department of Cognitive Sciences, University of California, Irvine, Irvine, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9066-6989
  5. Stephen V Mahler

    Department of Neurobiology and Behavior, University of California, Irvine, Irvine, United States
    Competing interests
    No competing interests declared.
  6. Kate M Wassum

    Department of Psychology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    Kate M Wassum, Reviewing editor, eLife.
  7. Sean B Ostlund

    Department of Anesthesiology and Perioperative Care, University of California, Irvine, Irvine, United States
    For correspondence
    sostlund@uci.edu
    Competing interests
    No competing interests declared.

Funding

National Institute of Mental Health (106972)

  • Kate M Wassum
  • Sean B Ostlund

National Institute of Diabetes and Digestive and Kidney Diseases (098709)

  • Sean B Ostlund

National Institute on Drug Abuse (029035)

  • Sean B Ostlund

National Institute on Aging (045380)

  • Sean B Ostlund

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

Ethics

Animal experimentation: All experimental procedures that involved rats were approved by the UC Irvine Institutional Animal Care and Use Committee (protocol AUP-17-68) and were in accordance with the National Research Council Guide for the Care and Use of Laboratory Animals.

Reviewing Editor

  1. Naoshige Uchida, Harvard University, United States

Publication history

  1. Received: November 10, 2018
  2. Accepted: May 19, 2019
  3. Accepted Manuscript published: May 20, 2019 (version 1)
  4. Version of Record published: June 4, 2019 (version 2)

Copyright

© 2019, Halbout et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Briac Halbout
  2. Andrew T Marshall
  3. Ali Azimi
  4. Mimi Liljeholm
  5. Stephen V Mahler
  6. Kate M Wassum
  7. Sean B Ostlund
(2019)
Mesolimbic dopamine projections mediate cue-motivated reward seeking but not reward retrieval in rats
eLife 8:e43551.
https://doi.org/10.7554/eLife.43551

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