Combination treatment with estradiol + progesterone acutely reduces heroin seeking. (A) Heroin seeking over the course of heroin self-administration, extinction, and cued reinstatement did not differ between groups prior to treatment. n = 8 estradiol; n = 7 estradiol + progesterone (n = 1 statistical outlier excluded, >2 standard deviations from mean). Sidak's post-hoc active versus inactive lever (+) P < 0.001 estradiol, (*) P < 0.05 estradiol + progesterone. (B) Number of heroin infusions over the course of self-administration also did not differ. (C) Heroin seeking on the first day of extinction was reduced by estradiol + progesterone treatment (15 µg/kg estradiol + 2 mg/kg progesterone, s.c.; Sigma-Aldrich, P0130) 30 min prior. Sidak's post-hoc estradiol versus estradiol + progesterone (**) P < 0.0001 (Unpaired, two-tailed t-test P < 0.05). (D) The extinction index did not differ between the combination treatment group versus estradiol alone. (E) Heroin seeking on the second day of extinction was not significantly different between treatments (P = 0.098). (F) Neither treatment on extinction day 1 altered relapse rates on the cued reinstatement test. All data are mean ± SEM. Gray bars = inactive presses nested within active presses.
