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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-02-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/52694 |
| _version_ | 1818017981322493952 |
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| author | Iris Bachmutsky Xin Paul Wei Eszter Kish Kevin Yackle |
| author_facet | Iris Bachmutsky Xin Paul Wei Eszter Kish Kevin Yackle |
| author_sort | Iris Bachmutsky |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-14T07:33:55Z |
| format | Article |
| id | doaj.art-5e3790b104ee49f4ae43c67e30ee7a98 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:33:55Z |
| publishDate | 2020-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-5e3790b104ee49f4ae43c67e30ee7a982022-12-22T02:05:45ZengeLife 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 |
| 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 |
| title | 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_short | Opioids depress breathing through two small brainstem sites |
| title_sort | opioids depress breathing through two small brainstem sites |
| topic | opioid respiratory depression breathing preBötzinger Complex central pattern generator |
| url | https://elifesciences.org/articles/52694 |
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