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A diencephalic circuit in rats for opioid analgesia but not positive reinforcement

Author

Listed:
  • Maggie W. Waung

    (UCSF Weill Institute for Neurosciences, Department of Neurology, University of California)

  • Kayla A. Maanum

    (UCSF Weill Institute for Neurosciences, Department of Neurology, University of California)

  • Thomas J. Cirino

    (UCSF Weill Institute for Neurosciences, Department of Neurology, University of California)

  • Joseph R. Driscoll

    (UCSF Weill Institute for Neurosciences, Department of Neurology, University of California)

  • Chris O’Brien

    (Rutgers University)

  • Svetlana Bryant

    (Rutgers University)

  • Kasra A. Mansourian

    (UCSF Weill Institute for Neurosciences, Department of Neurology, University of California)

  • Marisela Morales

    (National Institute on Drug Abuse, Neuronal Networks Section, National Institutes of Health)

  • David J. Barker

    (Rutgers University
    National Institute on Drug Abuse, Neuronal Networks Section, National Institutes of Health)

  • Elyssa B. Margolis

    (UCSF Weill Institute for Neurosciences, Department of Neurology, University of California
    Neuroscience Graduate Program, University of California)

Abstract

Mu opioid receptor (MOR) agonists are potent analgesics, but also cause sedation, respiratory depression, and addiction risk. The epithalamic lateral habenula (LHb) signals aversive states including pain, and here we found that it is a potent site for MOR-agonist analgesia-like responses in rats. Importantly, LHb MOR activation is not reinforcing in the absence of noxious input. The LHb receives excitatory inputs from multiple sites including the ventral tegmental area, lateral hypothalamus, entopeduncular nucleus, and the lateral preoptic area of the hypothalamus (LPO). Here we report that LHb-projecting glutamatergic LPO neurons are excited by noxious stimulation and are preferentially inhibited by MOR selective agonists. Critically, optogenetic stimulation of LHb-projecting LPO neurons produces an aversive state that is relieved by LHb MOR activation, and optogenetic inhibition of LHb-projecting LPO neurons relieves the aversiveness of ongoing pain.

Suggested Citation

  • Maggie W. Waung & Kayla A. Maanum & Thomas J. Cirino & Joseph R. Driscoll & Chris O’Brien & Svetlana Bryant & Kasra A. Mansourian & Marisela Morales & David J. Barker & Elyssa B. Margolis, 2022. "A diencephalic circuit in rats for opioid analgesia but not positive reinforcement," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28332-6
    DOI: 10.1038/s41467-022-28332-6
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    References listed on IDEAS

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    1. Masayuki Matsumoto & Okihide Hikosaka, 2007. "Lateral habenula as a source of negative reward signals in dopamine neurons," Nature, Nature, vol. 447(7148), pages 1111-1115, June.
    2. Bo Li & Joaquin Piriz & Martine Mirrione & ChiHye Chung & Christophe D. Proulx & Daniela Schulz & Fritz Henn & Roberto Malinow, 2011. "Synaptic potentiation onto habenula neurons in the learned helplessness model of depression," Nature, Nature, vol. 470(7335), pages 535-539, February.
    3. Tianwen Huang & Shing-Hong Lin & Nathalie M. Malewicz & Yan Zhang & Ying Zhang & Martyn Goulding & Robert H. LaMotte & Qiufu Ma, 2019. "Identifying the pathways required for coping behaviours associated with sustained pain," Nature, Nature, vol. 565(7737), pages 86-90, January.
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