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An endogenous opioid circuit determines state-dependent reward consumption

Author

Listed:
  • Daniel C. Castro

    (University of Washington
    Washington University School of Medicine
    Washington University Pain Center, Washington University School of Medicine
    University of Washington)

  • Corinna S. Oswell

    (University of Washington
    University of Washington)

  • Eric T. Zhang

    (University of Washington
    University of Washington)

  • Christian E. Pedersen

    (University of Washington
    University of Washington)

  • Sean C. Piantadosi

    (University of Washington
    University of Washington)

  • Mark A. Rossi

    (University of Washington
    University of Washington)

  • Avery C. Hunker

    (University of Washington)

  • Anthony Guglin

    (Washington University School of Medicine
    Washington University Pain Center, Washington University School of Medicine)

  • Jose A. Morón

    (Washington University School of Medicine
    Washington University Pain Center, Washington University School of Medicine)

  • Larry S. Zweifel

    (University of Washington)

  • Garret D. Stuber

    (University of Washington
    University of Washington
    University of Washington)

  • Michael R. Bruchas

    (University of Washington
    Washington University School of Medicine
    Washington University Pain Center, Washington University School of Medicine
    University of Washington)

Abstract

µ-Opioid peptide receptor (MOPR) stimulation alters respiration, analgesia and reward behaviour, and can induce substance abuse and overdose1–3. Despite its evident importance, the endogenous mechanisms for MOPR regulation of consummatory behaviour have remained unknown4. Here we report that endogenous MOPR regulation of reward consumption in mice acts through a specific dorsal raphe to nucleus accumbens projection. MOPR-mediated inhibition of raphe terminals is necessary and sufficient to determine consummatory response, while select enkephalin-containing nucleus accumbens ensembles are engaged prior to reward consumption, suggesting that local enkephalin release is the source of the endogenous MOPR ligand. Selective modulation of nucleus accumbens enkephalin neurons and CRISPR–Cas9-mediated disruption of enkephalin substantiate this finding. These results isolate a fundamental endogenous opioid circuit for state-dependent consumptive behaviour and suggest alternative mechanisms for opiate modulation of reward.

Suggested Citation

  • Daniel C. Castro & Corinna S. Oswell & Eric T. Zhang & Christian E. Pedersen & Sean C. Piantadosi & Mark A. Rossi & Avery C. Hunker & Anthony Guglin & Jose A. Morón & Larry S. Zweifel & Garret D. Stub, 2021. "An endogenous opioid circuit determines state-dependent reward consumption," Nature, Nature, vol. 598(7882), pages 646-651, October.
    • Handle: RePEc:nat:nature:v:598:y:2021:i:7882:d:10.1038_s41586-021-04013-0
    DOI: 10.1038/s41586-021-04013-0
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    Cited by:

    1. Kelsey M. Vollmer & Lisa M. Green & Roger I. Grant & Kion T. Winston & Elizabeth M. Doncheck & Christopher W. Bowen & Jacqueline E. Paniccia & Rachel E. Clarke & Annika Tiller & Preston N. Siegler & B, 2022. "An opioid-gated thalamoaccumbal circuit for the suppression of reward seeking in mice," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. In-Jee You & Yeeun Bae & Alec R. Beck & Sora Shin, 2023. "Lateral hypothalamic proenkephalin neurons drive threat-induced overeating associated with a negative emotional state," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    3. Gregory J. Salimando & Sébastien Tremblay & Blake A. Kimmey & Jia Li & Sophie A. Rogers & Jessica A. Wojick & Nora M. McCall & Lisa M. Wooldridge & Amrith Rodrigues & Tito Borner & Kristin L. Gardiner, 2023. "Human OPRM1 and murine Oprm1 promoter driven viral constructs for genetic access to μ-opioidergic cell types," Nature Communications, Nature, vol. 14(1), pages 1-24, December.

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