Postretrieval corticosterone transiently impairs subsequent recall of contextual fear conditioning. a, Percentage of time spent freezing in the training context before training in fear conditioning (Baseline), during subsequent reactivation 48 h hence (48 h from Train), and 24 h after reactivation (72 h from Train). Reactivation was followed by injection of vehicle or corticosterone at the indicated dose (one-way ANOVA for 72 h time point, p < 0.001, F(3,28) = 10.06; post hoc Tukey's test, p < 0.01 for Cort 3 mg/kg vs vehicle, p < 0.001, for Cort 10 mg/kg vs vehicle, p = 0.65, for Cort 3 mg/kg vs Aniso, p = 0.96, for Cort 10 mg/kg vs Aniso, p < 0.001, for Aniso vs vehicle, p = 0.90, for Cort 3 mg/kg vs Cort 10 mg/kg). b, Subsequent contextual memory recall is blocked by higher doses of corticosterone, and this effect resembles that of anisomycin. A dose–response curve for corticosterone administered immediately after memory reactivation is shown. Bars represent percentage of freezing 72 h after training (24 h after memory reactivation) (one-way ANOVA, p < 0.0001, F(6,49) = 10.86; post hoc Tukey's test, vehicle vs no injection, p = 0.95, vs Cort 0.3 mg/kg, p = 0.11, vs Cort 1 mg/kg, p = 0.99, vs Cort 3 mg/kg, p < 0.05, vs Cort 10 mg/kg, p < 0.01, vs Aniso, p < 0.001). No Injection was significantly different from Aniso, Cort 3 mg/kg, and Cort 10 mg/kg (p < 0.001 for all) and not different from Vehicle, Cort 0.3 mg/kg, or Cort 1 mg/kg (p = 0.95, 0.15, and 0.92, respectively). Cort 3 mg/kg differed from vehicle, Cort 1 mg/kg, and No Injection (p < 0.05, 0.05, and 0.01, respectively) but did not differ from Cort 0.3 mg/kg or Aniso (p = 0.39 and 0.92, respectively). Similarly, Cort 10 mg/kg differed from vehicle, Cort 1 mg/kg, and No Injection (p < 0.01, 0.01, and 0.001, respectively) but did not differ from Cort 0.3 mg/kg or Aniso (p = 0.11 and 0.99, respectively). ∗p < 0.05 on post hoc Tukey's test versus vehicle and No Injection. c, Effect of corticosterone on subsequent memory recall is transient. Error bars represent freezing 120 h (5 d) after training (72 h after memory reactivation). When tested 72 h after reactivation, the anisomycin effect on subsequent recall remained, whereas that of corticosterone is no longer present (ANOVA main effect of drug, p < 0.01, F(2,21) = 7.72; post hoc Tukey's test vehicle vs Aniso, ∗p < 0.01, vehicle vs Cort, p = 0.34; Aniso vs Cort, p = 0.058). Although b and c were necessarily performed in separate experiments in different groups on different days and thus normalized to separate control groups, a Student's t test comparison between Cort 3 mg/kg at 24 h from b and Cort 3 mg/kg at 72 h from c revealed a p = 0.068, whereas a similar comparison of Aniso 150 mg/kg at 24 h from b and Aniso 150 mg/kg from c revealed a p = 0.94. n = 8 in all groups. Error bars represent SEM in all figures.