ArticleJournal of neuroimmunology2025
Gut microbiome depletion modulates cocaine-induced behavioral and transcriptional responses in female mice.
Article in Journal of neuroimmunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- GutGut microbes · 2026Article
- Translational Evidence of Immunomodulation by Addictive Drugs: Mechanisms and Therapeutic Targets.Journal of neuroimmunology · 2025Article
- 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
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Authors and funding
8 authors.
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Abstract
Cocaine use disorder is a chronic relapsing condition with no FDA-approved biological treatments. The gut microbiome has emerged as a key modulator of neurobehavioral responses to drugs of abuse, yet its role in female animals has been under studied. Here, we investigated the effects of gut microbiome depletion on cocaine-induced behavioral and transcriptional responses in female mice. Adult female C57BL/6 J mice were treated with a non-absorbable oral antibiotic (Abx) cocktail for two weeks to deplete the gut microbiome, followed by behavioral assays assessing locomotor sensitization and conditioned place preference (CPP) to cocaine. Abx-treated females displayed reduced locomotor sensitization and a shifted CPP dose-response curve, characterized by attenuated preference at higher cocaine doses. Transcriptional analysis of the nucleus accumbens (NAc) revealed that microbiome depletion suppressed cocaine-induced expression of immediate early genes (c-Fos, FosB, Nr4a1, Egr4) and altered dopamine-related (Drd1) and microglial (Cx3cr1) markers. These findings contrast with prior studies in males, where microbiome depletion enhanced cocaine-induced behavioral plasticity. The observed effects suggest distinct gut-brain signaling as an important contributor to cocaine reinforcement and neuroadaptations in females. This study provides novel insights into microbiome regulation of addiction-relevant behaviors and highlights the necessity of sex-specific investigations in neuropsychiatric disorders. Further research is needed to elucidate the molecular pathways linking gut dysbiosis to substance use vulnerability in females.
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