The effect of concurrent access to alcohol and oxycodone on self-administration and reinstatement in rats

Although polysubstance use is highly prevalent, preclinical studies that assess voluntary consumption of multiple substances at the same time are rather uncommon. Overlooking drug taking patterns commonly observed in humans may limit the translational value of preclinical models.

Here, we aimed to develop a model of polysubstance use that could be used to assess oral operant self-administration patterns under concurrent access to alcohol and the prescription opioid oxycodone.

After a training period where animals associated specific cues and levers with each drug, rats self-administered alcohol and oxycodone solutions concurrently in daily sessions. Oxycodone was then removed to assess potential changes in alcohol consumption. The role of cues and stress on alcohol consumption and oxycodone seeking was also examined under reinstatement conditions.

We found that females consumed more alcohol and oxycodone than males when given access to both drugs, and this effect on alcohol intake persisted when oxycodone was removed. Additionally, re-exposure to oxycodone cues in combination with the administration of the pharmacological stressor yohimbine drove reinstatement of oxycodone seeking in females but did not have a strong effect in males, possibly due to low levels of oxycodone intake during active self-administration in male rats. Additionally, yohimbine drove increased alcohol consumption, in line with prior findings from our group and others.

Taken together, this study demonstrates that rats will concurrently self-administer both oxycodone and alcohol in operant chambers, and this procedure can serve as a platform for future investigations in polysubstance use and relapse-like behavior.