Opioids depress breathing through two small brainstem sites
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
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
- Ronald L Calabrese, Emory University, United States
Publication history
- Received: October 12, 2019
- Accepted: February 17, 2020
- Accepted Manuscript published: February 19, 2020 (version 1)
- 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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