Gut microbiome correlates with altered striatal dopamine receptor expression in a model of compulsive alcohol seeking
Open accessAbstract
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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Vitamin and mineral deficiencies associated with opioid addiction have been well-described.
“Vitamin and mineral deficiencies associated with opioid addiction have been well-described (160–165).”
From A Biopsychosocial Overview of the Opioid Crisis: Considering Nutrition and Gastrointestinal Health (2019) · cites this paper as [164]
Gut microbiome alterations and impulsive behaviors influenced by striatal dopamine receptor expression have reduced alcohol seeking in animal models.
“Gut microbiome alterations and impulsive behaviors influenced by striatal dopamine receptor expression have reduced alcohol seeking in animal models (164).”
From A Biopsychosocial Overview of the Opioid Crisis: Considering Nutrition and Gastrointestinal Health (2019) · cites this paper as [164]
Cites
A human gut microbial gene catalogue established by metagenomic sequencing
MetaHIT Consortium, Qin, J., Li, R., Raes, J., Arumugam, M., Burgdorf, K. S., Manichanh, C., Nielsen, T., Pons, N., Levenez, F., et al. (2010) · Nature · doi:10.1038/nature08821 · Cited by 11,624 · see citing works
Klindworth, A., Pruesse, E., Schweer, T., Peplies, J., Quast, C., Horn, M., & Glöckner, F. O. (2013) · Nucleic Acids Research · doi:10.1093/nar/gks808 · Cited by 8,850 · see citing works
Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour
Cryan, J. F., & Dinan, T. G. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3346 · Cited by 4,572 · see citing works
Self-citationBravo, J. A., Forsythe, P., Chew, M. V., Escaravage, E., Savignac, H. M., Dinan, T. G., Bienenstock, J., & Cryan, J. F. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1102999108 · Cited by 3,888 · see citing works
Self-citationPsychobiotics: A novel class of psychotropic
Dinan, T. G., Stanton, C., & Cryan, J. F. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.05.001 · Cited by 1,287 · see citing works
Self-citationMinireview: Gut microbiota: The neglected endocrine organ
Clarke, G., Stilling, R. M., Kennedy, P. J., Stanton, C., Cryan, J. F., & Dinan, T. G. (2014) · Molecular Endocrinology · doi:10.1210/me.2014-1108 · Cited by 1,192 · see citing works
Self-citation2010 National and State Costs of Excessive Alcohol Consumption
Sacks, J. J., Gonzales, K. R., Bouchery, E. E., Tomedi, L. E., & Brewer, R. D. (2015) · American Journal of Preventive Medicine · doi:10.1016/j.amepre.2015.05.031 · Cited by 1,180 · see citing works
Evidence for Addiction-like Behavior in the Rat
Deroche-Gamonet, V., Belin, D., & Piazza, P. V. (2004) · Science · doi:10.1126/science.1099020 · Cited by 1,135 · see citing works
The microbiome-gut-brain axis in health and disease
Dinan, T. G., & Cryan, J. F. (2017) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2016.09.007 · Cited by 1,111 · see citing works
Self-citationControl of brain development, function, and behavior by the microbiome
Sampson, T. R., & Mazmanian, S. K. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.04.011 · Cited by 1,093 · see citing works
Leclercq, S., Matamoros, S., Cani, P. D., Neyrinck, A. M., Jamar, F., Stärkel, P., Windey, K., Tremaroli, V., Bäckhed, F., Verbeke, K., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1415174111 · Cited by 972 · see citing works
Colonic microbiome is altered in alcoholism
Mutlu, E. A., Gillevet, P. M., Rangwala, H., Sikaroodi, M., Naqvi, A., Engen, P. A., Kwasny, M., Lau, C. K., & Keshavarzian, A. (2012) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00380.2011 · Cited by 775 · see citing works
Collective unconscious: How gut microbes shape human behavior
Dinan, T. G., Stilling, R. M., Stanton, C., & Cryan, J. F. (2015) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2015.02.021 · Cited by 571 · see citing works
Self-citationIntestinal microbiota contributes to individual susceptibility to alcoholic liver disease
Llopis, M., Cassard, A., Wrzosek, L., Boschat, L., Bruneau, A., Ferrere, G., Puchois, V., Martin, J., Lepage, P., Roy, T. L., et al. (2015) · Gut · doi:10.1136/gutjnl-2015-310585 · Cited by 562 · see citing works
Bull–Otterson, L., Feng, W., Kirpich, I., Wang, Y., Qin, X., Liu, Y., Gobejishvili, L., Joshi‐Barve, S., Ayvaz, T., Petrosino, J. F., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0053028 · Cited by 543 · see citing works
Bajaj, J. S., Hylemon, P. B., Ridlon, J. M., Heuman, D. M., Daita, K., White, M. B., Monteith, P., Noble, N. A., Sikaroodi, M., & Gillevet, P. M. (2012) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00152.2012 · Cited by 525 · see citing works
The microbiome: a key regulator of stress and neuroinflammation
Rea, K., Dinan, T. G., & Cryan, J. F. (2016) · Neurobiology of Stress · doi:10.1016/j.ynstr.2016.03.001 · Cited by 508 · see citing works
Self-citationThe microbiota-gut-brain axis: neurobehavioral correlates, health and sociality
Montiel-Castro, A. J., González-Cervantes, R. M., Bravo-Ruiseco, G., & Pacheco-López, G. (2013) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2013.00070 · Cited by 413 · see citing works
Golubeva, A. V., Joyce, S. A., Moloney, G., Burokas, A., Sherwin, E., Arboleya, S., Flynn, I., Khochanskiy, D., Moya-Pérez, A., Peterson, V., et al. (2017) · EBioMedicine · doi:10.1016/j.ebiom.2017.09.020 · Cited by 364 · see citing works
Self-citationPersonality, Addiction, Dopamine: Insights from Parkinson's Disease
Dagher, A., & Robbins, T. W. (2009) · Neuron · doi:10.1016/j.neuron.2009.01.031 · Cited by 339 · see citing works
Recent developments in understanding the role of the gut microbiota in brain health and disease
Sherwin, E., Dinan, T. G., & Cryan, J. F. (2018) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13416 · Cited by 338 · see citing works
Self-citationThe role of neuroimmune signaling in alcoholism
Crews, F. T., Lawrimore, C. J., Walter, T. J., & Coleman, L. G. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.01.031 · Cited by 321 · see citing works
Leclercq, S., Cani, P. D., Neyrinck, A. M., Stärkel, P., Jamar, F., Mikolajczak, M., Delzenne, N. M., & de Timary, P. (2012) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2012.04.001 · Cited by 310 · see citing works
Crews, F. T., Qin, L., Sheedy, D. L., Vetreno, R. P., & Zou, J. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.09.030 · Cited by 295 · see citing works
Alterations of the Host Microbiome Affect Behavioral Responses to Cocaine
Kiraly, D. D., Walker, D. M., Calipari, E. S., Labonté, B., Issler, O., Peña, C. J., Ribeiro, E., Russo, S. J., & Nestler, E. J. (2016) · Scientific Reports · doi:10.1038/srep35455 · Cited by 264 · see citing works
Unbalanced neuronal circuits in addiction
Volkow, N. D., Wang, G.-J., Tomasi, D. G., & Baler, R. (2013) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2013.01.002 · Cited by 219 · see citing works
Leclercq, S., De Saeger, C., Delzenne, N., de Timary, P., & Stärkel, P. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.02.003 · Cited by 216 · see citing works
Collins, S. M., Kassam, Z., & Berčík, P. (2013) · Current Opinion in Microbiology · doi:10.1016/j.mib.2013.06.004 · Cited by 206 · see citing works
Reappraising striatal D1- and D2-neurons in reward and aversion
Soares‐Cunha, C., Coimbra, B., Sousa, N., & Rodrigues, A. J. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.05.021 · Cited by 190 · see citing works
Microbial regulation of microRNA expression in the amygdala and prefrontal cortex
Hoban, A. E., Stilling, R. M., M. Moloney, G., Moloney, R. D., Shanahan, F., Dinan, T. G., Cryan, J. F., & Clarke, G. (2017) · Microbiome · doi:10.1186/s40168-017-0321-3 · Cited by 177 · see citing works
Self-citationThe link between inflammation, bugs, the intestine and the brain in alcohol dependence
Leclercq, S., de Timary, P., Delzenne, N. M., & Stärkel, P. (2017) · Translational Psychiatry · doi:10.1038/tp.2017.15 · Cited by 174 · see citing works
Toll-like receptor signaling and stages of addiction
Crews, F. T., Walter, T. J., Coleman, L. G., & Vetreno, R. P. (2017) · Psychopharmacology · doi:10.1007/s00213-017-4560-6 · Cited by 159 · see citing works
Striatal D1 and D2 signaling differentially predict learning from positive and negative outcomes
Cox, S. M. L., Frank, M. J., Larcher, K. M.-H., Fellows, L. K., Clark, C. A., Leyton, M., & Dagher, A. (2015) · NeuroImage · doi:10.1016/j.neuroimage.2014.12.070 · Cited by 144 · see citing works
Dunphy-Doherty, F., O'Mahony, S. M., Peterson, V. L., O'Sullivan, O., Crispie, F., Cotter, P. D., Wigmore, P., King, M. V., Cryan, J. F., & Fone, K. C. F. (2018) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2017.10.024 · Cited by 124 · see citing works
Self-citationThe global economic burden of alcohol: a review and some suggestions
Geiger, B. B. (2006) · Drug and Alcohol Review · doi:10.1080/09595230600944479 · Cited by 113 · see citing works
Wang, F., Simen, A. A., Arias, A. J., Lu, Q., & Zhang, H. (2012) · Human Genetics · doi:10.1007/s00439-012-1251-6 · Cited by 82 · see citing works
A role for the peripheral immune system in the development of alcohol use disorders?
de Timary, P., Stärkel, P., Delzenne, N. M., & Leclercq, S. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.04.013 · Cited by 80 · see citing works
The role of the gut–brain axis in alcohol use disorders
Gorky, J. M., & Schwaber, J. S. (2015) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2015.06.013 · Cited by 79 · see citing works
Individualised treatment in alcohol-dependent patients
Mann, K. F., & Hermann, D. (2010) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-010-0153-7 · Cited by 76 · see citing works
The microbiota, the gut and the brain in eating and alcohol use disorders: A ‘Ménage à Trois’?
Temko, J. E., Bouhlal, S., Farokhnia, M., Lee, M. R., Cryan, J. F., & Leggio, L. (2017) · Alcohol and Alcoholism · doi:10.1093/alcalc/agx024 · Cited by 76 · see citing works
Drunk bugs: Chronic vapour alcohol exposure induces marked changes in the gut microbiome in mice
Peterson, V. L., Jury, N. J., Cabrera‐Rubio, R., Draper, L. A., Crispie, F., Cotter, P. D., Dinan, T. G., Holmes, A., & Cryan, J. F. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.01.049 · Cited by 75 · see citing works
Self-citationSocial costs of illegal drugs, alcohol and tobacco in the European Union: A systematic review
Barrio, P., Reynolds, J., García‐Altés, A., Gual, A., & Anderson, P. (2017) · Drug and Alcohol Review · doi:10.1111/dar.12504 · Cited by 68 · see citing works
Reframing the Teenage Wasteland: Adolescent Microbiota-Gut-Brain Axis
Neufeld, K. M., Luczynski, P., Dinan, T. G., & Cryan, J. F. (2016) · The Canadian Journal of Psychiatry · doi:10.1177/0706743716635536 · Cited by 57 · see citing works
Self-citationPrediction of striatal D2 receptor binding by DRD2/ANKK1 TaqIA allele status
Eisenstein, S. A., Bogdan, R., Love-Gregory, L. D., Corral-Frías, N. S., Koller, J. M., BLACK, K. J., Moerlein, S. M., Perlmutter, J. S., Barch, D. M., & Hershey, T. G. (2016) · Synapse · doi:10.1002/syn.21916 · Cited by 54 · see citing works
A dysbiotic subpopulation of alcohol-dependent subjects
de Timary, P., Leclercq, S., Stärkel, P., & Delzenne, N. M. (2015) · Gut Microbes · doi:10.1080/19490976.2015.1107696 · Cited by 41 · see citing works
A preclinical model for identifying rats at risk of alcohol use disorder
Jadhav, K. S., Magistretti, P. J., Halfon, O., Augsburger, M. P., & Boutrel, B. (2017) · Scientific Reports · doi:10.1038/s41598-017-09801-1 · Cited by 38 · see citing works
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Cryan, J. F., O'Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., Codagnone, M. G., Cussotto, S., Fulling, C., Golubeva, A. V., et al. (2019) · Physiological Reviews · doi:10.1152/physrev.00018.2018 · Cited by 5,286 · see citing works
Self-citationLeclercq, S., Le Roy, T., Furgiuele, S., Coste, V., Bindels, L. B., Leyrolle, Q., Neyrinck, A. M., Quoilin, C., Amadieu, C., Petit, G., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108238 · Cited by 178 · see citing works
Zhao, W., Hu, Y., Li, C., Li, N., Zhu, S., Tan, X., Li, M., Zhang, Y., Xu, Z., Ding, Z., et al. (2020) · BioFactors · doi:10.1002/biof.1567 · Cited by 75 · see citing works
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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
- ORCID
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2018-10
- Volume
- 141
- Pages
- 249-259
- ISSN
- 0028-3908 (ISSN-L)
- OpenAlex
- W2889413110
- Semantic Scholar
- 7c9f39dd20b4a5b1da16cac7491eb2340026d6d5
- 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
- green
- serval.unil.ch
- Licence
- cc-by-nc-nd
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- 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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