RU-505 restored cognitive function in Tg6799 mice. (A) Freezing behavior was measured before electric foot shock during the training day to assess the basal freezing tendency of each group of mice. (n = 8–10 mice per group). (B) Contextual memory was assessed by measuring freezing behavior upon reexposure to the training chamber 24 h after fear conditioning training. (*, P < 0.05; **, P < 0.01; n = 8–10 mice per group). Results are from two independent experiments. (C–E) Spatial learning and memory retention of WT and Tg6799 mice was assessed using the Barnes maze after 3 mo of treatment with RU-505 or vehicle. One target hole was connected to a hidden escape chamber. (C) During training trials, latency to poke the target hole was measured. Significance was assessed using two-way ANOVA analysis with repeated measure (WT/vehicle vs. Tg6799/vehicle: F_[1,120] = 40.47; P < 0.001; Tg6799/vehicle vs. Tg6799/RU-505: F_[1,108] = 11.97; P < 0.01; n = 10–14 mice per group). Differences in latency were assessed by Bonferroni post hoc analysis. (D–F) During the Barnes maze probe trial, latency to reach the closed target hole (D), number of visits to the target hole (E), and total traveled distance (F) were measured ([E] *, P < 0.05; **, P < 0.01; ***, P < 0.001; n = 10–14 mice per group; [F] ***, P < 0.001; n = 10–14 mice per group). All results of the Barnes maze are from three independent experiments.