Temporal pattern of oxycodone self-administration in mice

Opioids, including oxycodone, are effective at providing analgesia to patients suffering from pain but carry with them the risk of abuse. Rodent models of self-administration are utilized to evaluate the motivational drive of subjects to seek rewarding substances, including the opioid oxycodone, or to evaluate novel therapeutic interventions to prevent seeking of rewarding substances. Self-administration studies examine complex integrated behaviors and many factors contribute to each subject's drive to seek potentially rewarding substances. Here, we report on an often-overlooked factor, namely, the time of day when each subject has access to the rewarding substance. Rodents, including commonly utilized laboratory mice and rats, are active during the dark phase of the circadian cycle, in contrast to the daytime hours when experiments are typically conducted in laboratory settings. In the present study, we observed significantly different oxycodone-seeking behavior between mice who had access to self-administer oxycodone overnight as compared to during the day. Female mice increased their seeking of 30 and 200 mg/l oral oxycodone, while no difference was observed when the concentration was 1000 mg/l, or when only water was offered. These results support that the time of day that subjects can access reward may have a substantial impact on their seeking behaviors, representing an important and overlooked variable in the preclinical modeling of addiction and its interventions.