Conclusion
The glucocorticoid antagonist PT150 reduces shock-induced fentanyl seeking, suggesting it may be effective against stress-induced relapse, although the sex difference in response may need further exploration.
Methods
Adult male and female Sprague-Dawley rats were trained to self-administer fentanyl (2.5 μg/kg/infusion, i.v.) in a model of escalation. Rats then received 7 days of abstinence, followed by extinction; PT150 (0, 50 or 100 mg/kg in Nutella®; p.o.) treatment started on the first day of extinction training and continued daily until the end of the study. Following 14 days of extinction, rats were tested for reinstatement following footshock and yohimbine (0, 1, or 2 mg/kg; i.p.), tested in counterbalanced order; PT150 or placebo treatment occurred prior to each extinction and reinstatement session.
Results
Prior to initiation of PT150 treatment, females self-administered greater levels of fentanyl during 1-h sessions compared to males; however, when switched to 6-h sessions, males and females self-administered similar levels of fentanyl and showed a similar escalation of intake over time. PT150 had no effect on extinction of self-administration. While both footshock and yohimbine reinstated fentanyl seeking, only footshock-induced reinstatement was decreased by PT150 (50 and 100 mg/kg). The effect of PT150 on footshock-induced reinstatement was driven primarily by males.