Opioids depress breathing through two small brainstem sites

  1. Iris Bachmutsky
  2. Xin Paul Wei
  3. Eszter Kish
  4. Kevin Yackle  Is a corresponding author
  1. University of California, San Francisco, United States

Abstract

The rates of opioid overdose in the United States quadrupled between 1999 and 2017, reaching a staggering 130 deaths per day. This health epidemic demands innovative solutions that require uncovering the key brain areas and cell types mediating the cause of overdose— opioid-induced respiratory depression. Here, we identify two primary changes to murine breathing after administering opioids. These changes implicate the brainstem's breathing circuitry which we confirm by locally eliminating the µ-Opioid receptor. We find the critical brain site is the preBötzinger Complex, where the breathing rhythm originates, and use genetic tools to reveal that just 70-140 neurons in this region are responsible for its sensitivity to opioids. Future characterization of these neurons may lead to novel therapies that prevent respiratory depression while sparing analgesia.

Data availability

Summary data generated in this study are included as a supplemental supporting file. All Matlab code and an example data are posted on Github: https://github.com/YackleLab/Opioids-depress-breathing-through-two-small-brainstem-sites

Article and author information

Author details

  1. Iris Bachmutsky

    Department of Physiology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Xin Paul Wei

    Department of Physiology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Eszter Kish

    Department of Physiology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Kevin Yackle

    Department of Physiology, University of California, San Francisco, San Francisco, United States
    For correspondence
    Kevin.Yackle@ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1870-2759

Funding

NIH Office of the Director (DP5-OD023116)

  • Kevin Yackle

University of California, San Francisco (Program for Breakthrough Biomedical Research)

  • Kevin Yackle

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

Reviewing Editor

  1. Ronald L Calabrese, Emory University, United States

Publication history

  1. Received: October 12, 2019
  2. Accepted: February 17, 2020
  3. Accepted Manuscript published: February 19, 2020 (version 1)
  4. Version of Record published: March 17, 2020 (version 2)

Copyright

© 2020, Bachmutsky 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. Iris Bachmutsky
  2. Xin Paul Wei
  3. Eszter Kish
  4. Kevin Yackle
(2020)
Opioids depress breathing through two small brainstem sites
eLife 9:e52694.
https://doi.org/10.7554/eLife.52694

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