Oxycodone self-administration and genetic background exert community-specific effects in the gut microbiome

Relevance: The gut microbiome and genetic factors contribute to OUD-related phenotypes, including oxycodone-induced analgesia and reward. Here, we examine the effects of genetic background and oxycodone self-administration on the fecal and cecal microbiomes in two genetically divergent, inbred rat strains (ACI/EurMcwi and M520/N).Goals: Previous work from our lab demonstrated that male and female rats from these strains reliably acquire and escalate oxycodone self-administration. Here, we compared how oxycodone self-administration altered the gut microbiome as compared to saline self-administration. Rats from the ACI/EurMcwi (n= 25F/20M) and M520/N (n = 17F/14M) strains underwent an intravenous self-administration paradigm to measure the acquisition (ten 2-hr sessions) and escalation (ten 12-hr sessions) of oxycodone use. Saline-administering counterparts were used as controls. To assess the effects of oxycodone on the gut microbiome, fecal samples were collected one day following the last self-administration session, and cecal contents were collected two days after the last self-administration session. Bacterial profiles were determined by broad-range amplification and sequence analysis of 16S rRNA genes. Amplicons were generated using primers that target the V3V4 variable region of the 16S gene.