Sex differences in responsiveness to the prescription opioid oxycodone in mice

• Male and female mice acquire similar oxycodone conditioned place preference.
• Oxycodone produces modestly different locomotor activation in males and females.
• Oxycodone produces greater analgesia in males than in females at higher doses.

Over-prescription and increased nonmedical use of oxycodone has become a major concern. Despite its increased use, preclinical data concerning oxycodone's effects are still limited, especially in rodent models. To address this, we examined oxycodone's effects on place preference, locomotor activation, corticosterone levels, and thermal analgesia across a range of doses (between 0.3 and 10 mg/kg) in gonadally intact, adult male and female C57BL/6J mice. Males and females showed oxycodone-induced conditioned place preference and did not show significant between-sex differences in their place preference behavior. During both CPP conditioning sessions and open field assay, locomotor activity was increased by 1, 3, and 10 mg/kg oxycodone in females and by 3 and 10 mg/kg oxycodone in males. Plasma corticosterone levels were higher in females (compared to males) at baseline as well as following acute oxycodone injection and open field testing. The time course of oxycodone-induced analgesia was similar in males and females, however the total antinociceptive effect (AUC0 − 120 min) was larger in males compared to females at the highest dose tested (10 mg/kg). Taken together, these data suggest that male and female mice are modestly different in their responses to oxycodone.