Cited by 101Neurotransmitter Receptor Influence on BehaviorGut microbiota and healthSubstance Abuse Treatment and Outcomes

Gut microbiome correlates with altered striatal dopamine receptor expression in a model of compulsive alcohol seeking

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Jadhav, Kshitij S., Peterson, Veronica L., Halfon, Olivier, Ahern, Grace, Fouhy, Fiona, Stanton, Catherine, Dinan, Timothy G., Cryan, John F. +1 more·2018·Neuropharmacology

Abstract

Identifying biological markers predicting vulnerability to develop excessive alcohol consumption may lead to a real improvement of clinical care. With converging evidence suggesting that gut microbiome is capable of influencing brain and behavior, this study aimed at investigating whether changes in gut microbiome composition is associated with conditioned responses to alcohol. We trained Wistar rats to self-administer alcohol for a prolonged period before screening those exhibiting uncontrolled alcohol seeking and taking by modeling diagnostic criteria for AUD: inability to abstain during a signaled period of reward unavailability, increased motivation assessed in a progressive effortful task and persistent alcohol intake despite aversive foot shocks. Based on addiction criteria scores, rats were assigned to either Vulnerable or Resilient groups. Vulnerable rats not only displayed increased impulsive and compulsive behaviors, but also displayed increased relapse after abstinence and increased sensitivity to baclofen treatments compared to resilient animals. Then, rats underwent a 3-month wash out period before sacrifice. Dorsal striatum was collected to assess dopamine receptor mRNA expression, and 16S microbiome sequencing was performed on caecal contents. Multiple significant correlations were found between gut microbiome and impulsivity measures, as well as augmentations in striatal Dopamine 1 receptor (D1R) and reductions in D2R as vulnerability to AUD increased. Therefore, using a singular translational approach based on biobehavioral dispositions to excessive alcohol seeking without heavy intoxication, our observations suggests an association between gut microbiome composition and these specific "at risk" behavioral traits observed in our translationally relevant model.

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Crossref · 10.1016/j.neuropharm.2018.08.026

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Authors
Jadhav, K. S., Peterson, V. L., Halfon, O., Ahern, G., Fouhy, F., Stanton, C., Dinan, T. G., Cryan, J. F., & Boutrel, B.
Affiliations
  • Centre Hospitalier Universitaire Vaudois (CH)
  • University College Cork (IE)
  • Teagasc - The Irish Agriculture and Food Development Authority (IE)
Corresponding author
  • Cryan, John F.
  • Boutrel, Benjamin
Venue
Neuropharmacology
Publisher
Elsevier BV
Published
2018-10
Volume
141
Pages
249-259
ISSN
0028-3908 (ISSN-L)
OpenAlex
W2889413110
Cited by
101
References
46
Citations by year
2026: 4 · 2025: 10 · 2024: 20 · 2023: 15 · 2022: 17 · 2021: 13 · 2020: 11 · 2019: 11
FWCI
3.98
Type
journal article
Language
en
Open access
Locations
  • Neuropharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • SERVAL (Université de Lausanne) (acceptedVersion, cc-by-nc-nd)
  • IRIS (submittedVersion, cc-by-nc-nd)
Funders
  • APC
  • Science Foundation Ireland (12/RC/2273)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
Keywords
gut microbiota, alcoholism, dopamine receptors, dopamine D1 receptor, dopamine D2 receptor, dorsal striatum, impulsivity, addiction vulnerability, alcohol self-administration, cecal microbiota, 16S rRNA gene sequencing
MeSH terms
Gastrointestinal Microbiome, Ethanol, Animals, Baclofen, Cecum, Compulsive Behavior, Corpus Striatum, Extinction, Psychological, Male, Motivation, Self Administration, Receptors, Dopamine D1, Receptors, Dopamine D2, Rats, Drug-Seeking Behavior

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