Opioids depress breathing through two small brainstem sites

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 depre...

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Main Authors:	Iris Bachmutsky, Xin Paul Wei, Eszter Kish, Kevin Yackle
Format:	Article
Language:	English
Published:	eLife Sciences Publications Ltd 2020-02-01
Series:	eLife
Subjects:	opioid respiratory depression breathing preBötzinger Complex central pattern generator
Online Access:	https://elifesciences.org/articles/52694

id	doaj-5e3790b104ee49f4ae43c67e30ee7a98
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spelling	doaj-5e3790b104ee49f4ae43c67e30ee7a982021-05-05T20:50:45ZengeLife Sciences Publications LtdeLife2050-084X2020-02-01910.7554/eLife.52694Opioids depress breathing through two small brainstem sitesIris Bachmutsky0Xin Paul Wei1Eszter Kish2Kevin Yackle3https://orcid.org/0000-0003-1870-2759Department of Physiology, University of California-San Francisco, San Francisco, United States; Neuroscience Graduate Program, University of California-San Francisco, San Francisco, United StatesDepartment of Physiology, University of California-San Francisco, San Francisco, United States; Biomedical Sciences Graduate Program, University of California-San Francisco, San Francisco, United StatesDepartment of Physiology, University of California-San Francisco, San Francisco, United States; Neuroscience Graduate Program, University of California-San Francisco, San Francisco, United StatesDepartment of Physiology, University of California-San Francisco, San Francisco, United StatesThe 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.https://elifesciences.org/articles/52694opioid respiratory depressionbreathingpreBötzinger Complexcentral pattern generator
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Iris Bachmutsky Xin Paul Wei Eszter Kish Kevin Yackle
spellingShingle	Iris Bachmutsky Xin Paul Wei Eszter Kish Kevin Yackle Opioids depress breathing through two small brainstem sites eLife opioid respiratory depression breathing preBötzinger Complex central pattern generator
author_facet	Iris Bachmutsky Xin Paul Wei Eszter Kish Kevin Yackle
author_sort	Iris Bachmutsky
title	Opioids depress breathing through two small brainstem sites
title_short	Opioids depress breathing through two small brainstem sites
title_full	Opioids depress breathing through two small brainstem sites
title_fullStr	Opioids depress breathing through two small brainstem sites
title_full_unstemmed	Opioids depress breathing through two small brainstem sites
title_sort	opioids depress breathing through two small brainstem sites
publisher	eLife Sciences Publications Ltd
series	eLife
issn	2050-084X
publishDate	2020-02-01
description	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.
topic	opioid respiratory depression breathing preBötzinger Complex central pattern generator
url	https://elifesciences.org/articles/52694
work_keys_str_mv	AT irisbachmutsky opioidsdepressbreathingthroughtwosmallbrainstemsites AT xinpaulwei opioidsdepressbreathingthroughtwosmallbrainstemsites AT eszterkish opioidsdepressbreathingthroughtwosmallbrainstemsites AT kevinyackle opioidsdepressbreathingthroughtwosmallbrainstemsites
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Opioids depress breathing through two small brainstem sites

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