Figure 1.

PEPA facilitates extinction learning. A, Experimental design for B–D. Mice were trained for the contextual fear conditioning and tested 24 h (extinction training) and 72 h (extinction test) later. PEPA or vehicle (V) was injected (i.p.) 15 min before extinction training. B, C, Dose-dependent reduction of freezing time during extinction training (B) and extinction test (C). Data represent mean + SEM (n = 9–11 for each group). D, Reduction in freezing time between the extinction training and extinction test based on the data in B and C. E, Experimental design for F. Mice were trained for the contextual fear conditioning and tested 72 h later (test) without extinction training. PEPA or vehicle were injected 24 h after conditioning. F, PEPA did not reduce freezing time in the test when extinction training was skipped (n = 10 each). *Statistically significant (p = 0.002 vs V in B; p < 0.001 vs V in C, and p = 0.005 vs V in D, Bonferroni/Dunn test). G, H, Changes in freezing time during the 360 s extinction training (G) and test (H) in groups injected with PEPA (30 mg/kg, n = 11) or vehicle (n = 9). Data used in B and C were reanalyzed for the time course of changes in freezing time (bin = 60 s). *Statistically significant (p = 0.002, 0.002, and 0.001 for bins 3–5, respectively, vs V in G, and p < 0.02 for all vs V in H, two-tailed Student's t test).