Oxycodone is one of the most widely prescribed painkillers in the USA. However, its use is complicated by high abuse potential. As sex differences have been described in drug addiction, the present study tested for sex differences in intravenous oxycodone self-administration in rats.

Male and female Sprague-Dawley rats were implanted with jugular vein catheters and trained to self-administer oxycodone (0.03 mg/kg/infusion) under fixed ratio 1 (FR1), FR2, and FR5 schedules of reinforcement followed by a dose-response study to assess sensitivity to the reinforcing effects of oxycodone. In separate rats, sucrose pellet self-administration was assessed under an FR1 schedule to determine whether sex differences in oxycodone self-administration could be generalized across reinforcers. In separate rats, oxycodone distribution to plasma and brain was measured after intravenous drug delivery.

In the first 3 trials under an FR1 schedule of reinforcement, male rats self-administered more oxycodone than females. In contrast, females self-administered more sucrose pellets. Under FR2 and FR5 schedules, no significant sex differences in oxycodone intake were observed, although female rats had significantly more inactive lever presses. Male and female rats showed similar inverted U-shaped dose-effect functions, with females tending to self-administer more oxycodone than males at higher doses. No significant sex differences were observed in plasma or brain oxycodone levels, suggesting that sex differences in oxycodone self-administration behavior were not due to pharmacokinetics.

Our results suggest subtle sex differences in oxycodone self-administration, which may influence the abuse liability of oxycodone and have ramifications for prescription opioid addiction treatment.