ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2024
Microbial short-chain fatty acids regulate drug seeking and transcriptional control in a model of cocaine seeking.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- The Gut Microbiota in Addiction Biology: A Systematic Review of Substance-Induced Dysbiosis and Gut-Brain Axis Alterations.Medical sciences (Basel, Switzerland) · 2026Pooled it
- GutGut microbes · 2026Article
- Microbiome-derived metabolites shape CD4+ T cell differentiation and immune aging in HIV-1 infection.JCI insight · 2026Article
- Behavioral flexibility and gut microbiome as potential predictors of oral oxycodone self-administration.bioRxiv : the preprint server for biology · 2026Article
- Microbiome-Derived Metabolites Shape CD4bioRxiv : the preprint server for biology · 2026Article
- Brief antibiotics exposure during adolescence produces persistent effects on the microbiome and fentanyl-seeking during adulthood in rats.Frontiers in behavioral neuroscience · 2026Article
- Metabolomic and gut microbial biomarkers of smoking cessation treatment in long-term drug therapy: a study protocol for a randomized controlled trial.Frontiers in psychiatry · 2026Article
- From bugs to behavior: targeting the gut-brain interface for addiction therapeutics.Gut microbes · 2025Review
- Brief exposure to oral antibiotics has age-dependent effects on morphine reward and gene expression in the medial prefrontal cortex of adolescent and adult mice.Brain, behavior, and immunity · 2025Article
- Microbiome-derived metabolites in substance use disorders: Mechanisms and implications.Annals of the New York Academy of Sciences · 2025Review
- Integrative systems biology approaches for analyzing microbiome dysbiosis and species interactions.Briefings in bioinformatics · 2025Review
- Gut microbiome depletion modulates cocaine-induced behavioral and transcriptional responses in female mice.Journal of neuroimmunology · 2025Article
- The Bidirectional Interplay Between Substances of Abuse and Gut Microbiome Homeostasis.Life (Basel, Switzerland) · 2025Review
- The Legalome: Microbiology, Omics and Criminal Justice.Microbial biotechnology · 2025Article
- The Gut Microbiome Regulates the Psychomotor Effects and Context-Dependent Rewarding Responses to Cocaine in Germ-Free and Antibiotic-Treated Animal Models.Microorganisms · 2025Article
- A Comprehensive 4-layeredCurrent pharmaceutical biotechnology · 2025Article
- Intragastric administration of short chain fatty acids greatly reduces voluntary ethanol intake in rats.Scientific reports · 2024Article
- Colony-stimulating factor 2 (CSF2) as a gut microbiome dependent immune factor that alters molecular and behavioral responses to cocaine in male mice.Brain, behavior, and immunity · 2024Article
- The Gut-Brain Axis in Opioid Use Disorder: Exploring the Bidirectional Influence of Opioids and the Gut Microbiome-A Comprehensive Review.Life (Basel, Switzerland) · 2024Review
- Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
Cocaine use disorder represents a public health crisis with no FDA-approved medications for its treatment. A growing body of research has detailed the important connections between the brain and the resident population of bacteria in the gut, the gut microbiome, in psychiatric disease models. Acute depletion of gut bacteria results in enhanced reward in a mouse cocaine place preference model, and repletion of bacterially-derived short-chain fatty acid (SCFA) metabolites reverses this effect. However, the role of the gut microbiome and its metabolites in modulating cocaine-seeking behavior after prolonged abstinence is unknown. Given that relapse prevention is the most clinically challenging issue in treating substance use disorders, studies examining the effects of microbiome manipulations in relapse-relevant models are critical. Here, male Sprague-Dawley rats received either untreated water or antibiotics to deplete the gut microbiome and its metabolites. Rats were trained to self-administer cocaine and subjected to either within-session threshold testing to evaluate motivation for cocaine or 21 days of abstinence followed by a cue-induced cocaine-seeking task to model relapse behavior. Microbiome depletion did not affect cocaine acquisition on an fixed-ratio 1 schedule. However, microbiome-depleted rats exhibited significantly enhanced motivation for low dose cocaine on a within-session threshold task. Similarly, microbiome depletion increased cue-induced cocaine-seeking following prolonged abstinence and altered transcriptional regulation in the nucleus accumbens. In the absence of a normal microbiome, repletion of bacterially-derived SCFA metabolites reversed the behavioral and transcriptional changes associated with microbiome depletion. These findings suggest that gut bacteria, via their metabolites, are key regulators of drug-seeking behaviors, positioning the microbiome as a potential translational research target.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.