Figure 1.

Formation and extinction of stress-induced freezing. A, Normal conditioning, but impaired extinction of context-specific fear responses was observed in Pdyn^−/− mice. Enhanced freezing behavior elicited by footshock stress persisted during the four consecutive extinction trials in Pdyn^−/− animals, whereas wild-type mice showed an extinction of the fear response in the second extinction trial. PC, Preconditioning trial; E1–E4, extinction trial 1–4. *p < 0.05; **p < 0.01 significantly different from the value measured at the first extinction trial (one-way ANOVA followed by Dunnett's test; n = 10). B, When the animals were tested in a new environment in the presence of a stress associated cue, Pdyn^−/− animals showed an enhanced freezing during the tone presentation both 24 h and 6 days after the fear conditioning accompanied by an impaired fear extinction. PC, Preconditioning trial; 24h, 24 h after conditioning: 6d, 6 days after conditioning. *p < 0.05; ***p < 0.001 significantly different from the value measured 24 h after the conditioning. ⁺⁺p < 0.01 significant difference between the genotypes on the same test day (two-way ANOVA followed by Bonferroni's t test; n = 10–8). C, The time spent with freezing in Penk1 or β-endorphin-null mutant animals was significantly enhanced 24 h after the fear conditioning in the first extinction trial, but not later on. PC, Preconditioning trial; E1–E4, extinction trial 1–4. **p < 0.01 significantly different from the value measured at the first extinction trial (E1) (one-way ANOVA followed by Dunnett's test; n = 10).