Behavioral flexibility, gut microbiome composition, and individual variability in oral oxycodone self-administration

In male and female Long-Evans rats, behavioral patterns of reinforced oral oxycodone self-administration are linked to higher oxycodone consumption, with three behavioral profiles emerging along this relationship.

• Why it matters: Individual differences in opioid intake may help explain why some animals escalate drug-taking beyond prescribed-like contexts, but the behavioral and gut-microbiome correlates are not well defined.
• What they did: Rats completed a contingency degradation task for behavioral flexibility before exposure, then underwent oral oxycodone self-administration; principal component analysis and hierarchical clustering related self-administration patterns to later intake.
• The result: Behavioral flexibility was negatively associated with subsequent oxycodone intake, and oral oxycodone exposure altered gut microbiome composition, with microbiome features linked to both behavioral flexibility and oxycodone intake.

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