Conclusions
The present study demonstrated the face validity of the extended access model of oxycodone self-administration by identifying sex differences in the escalation of oxycodone intake and pronounced changes in pain and affective states.
Results
Both male and female rats escalated their oxycodone intake over fourteen 12-h self-administration sessions. After escalation, female rats administered more drug than male rats. No differences in plasma oxycodone levels were identified, but males had a significantly higher level of oxycodone in the brain at 30 min. Extended access to oxycodone significantly decreased aggressive-like behavior and increased defensive-like behaviors when tested immediately after a 12-h self-administration session, followed by a rebound increase in aggressive-like behavior 12 h into withdrawal. Tests of mechanical nociception thresholds during withdrawal indicated pronounced hyperalgesia. No sex differences in irritability-like behavior or pain sensitivity were observed. Conclusions: The present study demonstrated the face validity of the extended access model of oxycodone self-administration by identifying sex differences in the escalation of oxycodone intake and pronounced changes in pain and affective states.