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Depletion of the Microbiome Alters the Recruitment of Neuronal Ensembles of Oxycodone Intoxication and Withdrawal
Substance use disorders have a complex etiology. Genetics, the environment, and behavior all play a role in the initiation, escalation, and relapse of drug use. Recently, opioid use disorder has become a national health crisis. One aspect of opioid addiction that has yet to be fully examined is the...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Society for Neuroscience
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242819/ https://www.ncbi.nlm.nih.gov/pubmed/32341122 http://dx.doi.org/10.1523/ENEURO.0312-19.2020 |
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author | Simpson, Sierra Kimbrough, Adam Boomhower, Brent McLellan, Rio Hughes, Marcella Shankar, Kokila de Guglielmo, Giordano George, Olivier |
author_facet | Simpson, Sierra Kimbrough, Adam Boomhower, Brent McLellan, Rio Hughes, Marcella Shankar, Kokila de Guglielmo, Giordano George, Olivier |
author_sort | Simpson, Sierra |
collection | PubMed |
description | Substance use disorders have a complex etiology. Genetics, the environment, and behavior all play a role in the initiation, escalation, and relapse of drug use. Recently, opioid use disorder has become a national health crisis. One aspect of opioid addiction that has yet to be fully examined is the effects of alterations of the microbiome and gut-brain axis signaling on central nervous system activity during opioid intoxication and withdrawal. The effect of microbiome depletion on the activation of neuronal ensembles was measured by detecting Fos-positive (Fos+) neuron activation during intoxication and withdrawal using a rat model of oxycodone dependence. Daily oxycodone administration (2 mg/kg) increased pain thresholds and increased Fos+ neurons in the basolateral amygdala (BLA) during intoxication, with a decrease in pain thresholds and increase in Fos+ neurons in the periaqueductal gray (PAG), central nucleus of the amygdala (CeA), locus coeruleus (LC), paraventricular nucleus of the thalamus (PVT), agranular insular cortex (AI), bed nucleus of the stria terminalis (BNST), and lateral habenula medial parvocellular region during withdrawal. Microbiome depletion produced widespread but region- and state-specific changes in neuronal ensemble activation. Oxycodone intoxication and withdrawal also increased functional connectivity among brain regions. Microbiome depletion resulted in a decorrelation of this functional network. These data indicate that microbiome depletion by antibiotics produces widespread changes in the recruitment of neuronal ensembles that are activated by oxycodone intoxication and withdrawal, suggesting that the gut microbiome may play a role in opioid use and dependence. Future studies are needed to better understand the molecular, neurobiological, and behavioral effects of microbiome depletion on addiction-like behaviors. |
format | Online Article Text |
id | pubmed-7242819 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Society for Neuroscience |
record_format | MEDLINE/PubMed |
spelling | pubmed-72428192020-05-22 Depletion of the Microbiome Alters the Recruitment of Neuronal Ensembles of Oxycodone Intoxication and Withdrawal Simpson, Sierra Kimbrough, Adam Boomhower, Brent McLellan, Rio Hughes, Marcella Shankar, Kokila de Guglielmo, Giordano George, Olivier eNeuro Research Article: New Research Substance use disorders have a complex etiology. Genetics, the environment, and behavior all play a role in the initiation, escalation, and relapse of drug use. Recently, opioid use disorder has become a national health crisis. One aspect of opioid addiction that has yet to be fully examined is the effects of alterations of the microbiome and gut-brain axis signaling on central nervous system activity during opioid intoxication and withdrawal. The effect of microbiome depletion on the activation of neuronal ensembles was measured by detecting Fos-positive (Fos+) neuron activation during intoxication and withdrawal using a rat model of oxycodone dependence. Daily oxycodone administration (2 mg/kg) increased pain thresholds and increased Fos+ neurons in the basolateral amygdala (BLA) during intoxication, with a decrease in pain thresholds and increase in Fos+ neurons in the periaqueductal gray (PAG), central nucleus of the amygdala (CeA), locus coeruleus (LC), paraventricular nucleus of the thalamus (PVT), agranular insular cortex (AI), bed nucleus of the stria terminalis (BNST), and lateral habenula medial parvocellular region during withdrawal. Microbiome depletion produced widespread but region- and state-specific changes in neuronal ensemble activation. Oxycodone intoxication and withdrawal also increased functional connectivity among brain regions. Microbiome depletion resulted in a decorrelation of this functional network. These data indicate that microbiome depletion by antibiotics produces widespread changes in the recruitment of neuronal ensembles that are activated by oxycodone intoxication and withdrawal, suggesting that the gut microbiome may play a role in opioid use and dependence. Future studies are needed to better understand the molecular, neurobiological, and behavioral effects of microbiome depletion on addiction-like behaviors. Society for Neuroscience 2020-05-21 /pmc/articles/PMC7242819/ /pubmed/32341122 http://dx.doi.org/10.1523/ENEURO.0312-19.2020 Text en Copyright © 2020 Simpson et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article: New Research Simpson, Sierra Kimbrough, Adam Boomhower, Brent McLellan, Rio Hughes, Marcella Shankar, Kokila de Guglielmo, Giordano George, Olivier Depletion of the Microbiome Alters the Recruitment of Neuronal Ensembles of Oxycodone Intoxication and Withdrawal |
title | Depletion of the Microbiome Alters the Recruitment of Neuronal Ensembles of Oxycodone Intoxication and Withdrawal |
title_full | Depletion of the Microbiome Alters the Recruitment of Neuronal Ensembles of Oxycodone Intoxication and Withdrawal |
title_fullStr | Depletion of the Microbiome Alters the Recruitment of Neuronal Ensembles of Oxycodone Intoxication and Withdrawal |
title_full_unstemmed | Depletion of the Microbiome Alters the Recruitment of Neuronal Ensembles of Oxycodone Intoxication and Withdrawal |
title_short | Depletion of the Microbiome Alters the Recruitment of Neuronal Ensembles of Oxycodone Intoxication and Withdrawal |
title_sort | depletion of the microbiome alters the recruitment of neuronal ensembles of oxycodone intoxication and withdrawal |
topic | Research Article: New Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242819/ https://www.ncbi.nlm.nih.gov/pubmed/32341122 http://dx.doi.org/10.1523/ENEURO.0312-19.2020 |
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