IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-28332-6.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-28332-6
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-28332-6?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Anton Ilango & Jason Shumake & Wolfram Wetzel & Henning Scheich & Frank W Ohl, 2013. "Electrical Stimulation of Lateral Habenula during Learning: Frequency-Dependent Effects on Acquisition but Not Retrieval of a Two-Way Active Avoidance Response," PLOS ONE, Public Library of Science, vol. 8(6), pages 1-8, June.
    2. Robyn Mary Brown & Jennifer Lynn Short & Andrew John Lawrence, 2010. "Identification of Brain Nuclei Implicated in Cocaine-Primed Reinstatement of Conditioned Place Preference: A Behaviour Dissociable from Sensitization," PLOS ONE, Public Library of Science, vol. 5(12), pages 1-13, December.
    3. Soo Hyun Yang & Esther Yang & Jaekwang Lee & Jin Yong Kim & Hyeijung Yoo & Hyung Sun Park & Jin Taek Jung & Dongmin Lee & Sungkun Chun & Yong Sang Jo & Gyeong Hee Pyeon & Jae-Yong Park & Hyun Woo Lee , 2023. "Neural mechanism of acute stress regulation by trace aminergic signalling in the lateral habenula in male mice," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    4. Hiroyuki Kawai & Youcef Bouchekioua & Naoya Nishitani & Kazuhei Niitani & Shoma Izumi & Hinako Morishita & Chihiro Andoh & Yuma Nagai & Masashi Koda & Masako Hagiwara & Koji Toda & Hisashi Shirakawa &, 2022. "Median raphe serotonergic neurons projecting to the interpeduncular nucleus control preference and aversion," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    5. Paul Leon Brown & Paul D Shepard, 2013. "Lesions of the Fasciculus Retroflexus Alter Footshock-Induced cFos Expression in the Mesopontine Rostromedial Tegmental Area of Rats," PLOS ONE, Public Library of Science, vol. 8(4), pages 1-9, April.
    6. Huanyuan Zhou & KongFatt Wong-Lin & Da-Hui Wang, 2018. "Parallel Excitatory and Inhibitory Neural Circuit Pathways Underlie Reward-Based Phasic Neural Responses," Complexity, Hindawi, vol. 2018, pages 1-20, April.
    7. Tommaso Ianni & Sedona N. Ewbank & Marjorie R. Levinstein & Matine M. Azadian & Reece C. Budinich & Michael Michaelides & Raag D. Airan, 2024. "Sex dependence of opioid-mediated responses to subanesthetic ketamine in rats," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    8. Robert C Wilson & Matthew R Nassar & Joshua I Gold, 2013. "A Mixture of Delta-Rules Approximation to Bayesian Inference in Change-Point Problems," PLOS Computational Biology, Public Library of Science, vol. 9(7), pages 1-18, July.
    9. Li Shen & Guang-Wei Zhang & Can Tao & Michelle B. Seo & Nicole K. Zhang & Junxiang J. Huang & Li I. Zhang & Huizhong W. Tao, 2022. "A bottom-up reward pathway mediated by somatostatin neurons in the medial septum complex underlying appetitive learning," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    10. Timo A. Nees & Na Wang & Pavel Adamek & Nadja Zeitzschel & Clement Verkest & Carmen Porta & Irina Schaefer & Julie Virnich & Selin Balkaya & Vincenzo Prato & Chiara Morelli & Valerie Begay & Young Jae, 2023. "Role of TMEM100 in mechanically insensitive nociceptor un-silencing," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    11. Pavel Shekhtmeyster & Erin M. Carey & Daniela Duarte & Alexander Ngo & Grace Gao & Nicholas A. Nelson & Charles L. Clark & Axel Nimmerjahn, 2023. "Multiplex translaminar imaging in the spinal cord of behaving mice," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28332-6. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.