Estradiol selectively enhances extinction memory retention without altering 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 = 7 vehicle (n = 1 statistical outlier excluded, >2 standard deviations from mean); n = 8 estradiol. Sidak's post-hoc active versus inactive lever (*) P < 0.01 vehicle, (+) P < 0.0001 estradiol. (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 not altered by estradiol treatment (15 µg/kg, s.c.; Sigma-Aldrich, E8875) 30 min prior. (D) The extinction index was significantly higher (indicating better extinction) in the estradiol group. Unpaired, two-tailed t-test (*) P < 0.05. (E) Heroin seeking on the second day of extinction was reduced by estradiol treatment the previous day. Unpaired, two-tailed t-test (**) P < 0.01. (F) Estradiol treatment on extinction day 1 did not alter relapse rates on the cued reinstatement test. All data are mean ± SEM. Gray bars = inactive presses nested within active presses.
