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Temporal Importance of Gut Microbiome Alterations in Cocaine Self-Administration

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title
Temporal Importance of Gut Microbiome Alterations in Cocaine Self-Administration
author
Boyer, Gregory
abstract
Cocaine use disorder remains a significant public health concern with no FDA-approved treatments. Recent studies have highlighted the gut microbiome as a potential therapeutic target due to its bidirectional communication with the brain. While previous studies have demonstrated that alterations to the microbiome can influence cocaine self-administration, the temporal significance of such changes remains poorly understood. This study aims to address this gap by investigating the impact of microbiome depletion during drug abstinence on cocaine-seeking behavior. Using a preclinical model, male and female Sprague-Dawley rats underwent 14 days of cocaine self-administration on an FR1 schedule of reinforcement, followed by a 21-day abstinence period, during which microbiome depletion was induced using a cocktail of broad- spectrum antibiotics. While no significant changes in cocaine-seeking behavior were observed in male rats, female rats exhibited reduced cocaine-seeking behavior in a light-cued reinstatement task following microbiome depletion. Molecular analysis of the NAc revealed no changes in Drd1, Drd1, or Fosb expression in females, suggesting that alternative molecular mechanisms targets may mediate the observed behavioral effects. These findings highlight the potential that further study of the interactions between the gut microbiome and substance use could yield novel therapeutic treatment strategies to reduce relapse risk.
subject
addiction
antibiotics
cocaine
dopamine
microbiome
self-administration
contributor
Kiraly, Drew (advisor)
Centanni, Samuel W. (committee member)
Weiner, Jeffrey L. (committee member)
date
2025-06-24T08:36:44Z (accessioned)
2025 (issued)
degree
Neuroscience – MS (discipline)
embargo
2030-05-17 (terms)
2030-05-17 (liftdate)
identifier
http://hdl.handle.net/10339/111066 (uri)
language
en (iso)
publisher
Wake Forest University
type
Thesis

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