Cited by 173Gut microbiota and healthGastrointestinal motility and disordersOpioid Use Disorder Treatment

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The gut microbiota mediates reward and sensory responses associated with regimen-selective morphine dependence

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Lee, Kevin, Vuong, Helen E., Nusbaum, David J., Hsiao, Elaine Y., Evans, Christopher J., Taylor, Anna M. W.·2018·Neuropsychopharmacology

DOI 10.1038/s41386-018-0211-9PMC PMC6224506

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Abstract

Opioid use for long-term pain management is limited by adverse side effects, such as hyperalgesia and negative affect. Neuroinflammation in the brain and spinal cord is a contributing factor to the development of symptoms associated with chronic opioid use. Recent studies have described a link between neuroinflammation and behavior that is mediated by a gut-brain signaling axis, where alterations in indigenous gut bacteria contribute to several inflammation-related psychopathologies. As opioid receptors are highly expressed within the digestive tract and opioids influence gut motility, we hypothesized that systemic opioid treatment will impact the composition of the gut microbiota. Here, we explored how opioid treatments, and cessation, impacts the mouse gut microbiome and whether opioid-induced changes in the gut microbiota influences inflammation-driven hyperalgesia and impaired reward behavior. Male C57Bl6/J mice were treated with either intermittent or sustained morphine. Using 16S rDNA sequencing, we describe changes in gut microbiota composition following different morphine regimens. Manipulation of the gut microbiome was used to assess the causal relationship between the gut microbiome and opioid-dependent behaviors. Intermittent, but not sustained, morphine treatment was associated with microglial activation, hyperalgesia, and impaired reward response. Depletion of the gut microbiota via antibiotic treatment surprisingly recapitulated neuroinflammation and sequelae, including reduced opioid analgesic potency and impaired cocaine reward following intermittent morphine treatment. Colonization of antibiotic-treated mice with a control microbiota restored microglial activation state and behaviors. Our findings suggest that differing opioid regimens uniquely influence the gut microbiome that is causally related to behaviors associated with opioid dependence.

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Authors: Lee, K., Vuong, H. E., Nusbaum, D. J., Hsiao, E. Y., Evans, C. J., & Taylor, A. M. W.
Affiliations: University of California, Los Angeles (US)
University of Alberta (CA)
Corresponding author: Taylor, Anna M. W.
ORCID: Lee, Kevin
Vuong, Helen E.
Nusbaum, David J.
Hsiao, Elaine Y.
Evans, Christopher J.
Taylor, Anna M. W.
Venue: Neuropsychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2018-09-10
Volume: 43
Issue: 13
Pages: 2606-2614
ISSN: 0893-133X (ISSN-L)
1740-634X
DOI: 10.1038/s41386-018-0211-9
PMC: PMC6224506
OpenAlex: W2890990778
Cited by: 172
References: 50
Citations by year: 2026: 6 · 2025: 19 · 2024: 19 · 2023: 26 · 2022: 34 · 2021: 26 · 2020: 26 · 2019: 15 · 2018: 1
FWCI: 6.05
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
Locations: Neuropsychopharmacology (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Alfred P. Sloan Foundation
American Pain Society
National Institute of Mental Health (F31MH090749)
National Institute on Drug Abuse (P50DA005010, DA 005010, K99DA040016)
National Institute of General Medical Sciences (K12GM106996)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
Keywords: gut microbiota, morphine dependence, opioid use disorder, neuroinflammation, microglial activation, hyperalgesia, opioid reward, cocaine reward, gut-brain axis, antibiotic-induced microbiota depletion, chronic opioid use
MeSH terms: Gastrointestinal Microbiome, Analgesics, Opioid, Animals, Intestinal Absorption, Male, Mice, Inbred C57BL, Morphine, Morphine Dependence, Reward, Mice

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The gut microbiota mediates reward and sensory responses associated with regimen-selective morphine dependence

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