Figure 1.

A, B, Spatial learning and memory in adult wild-type and CRF₁-CKO mice that were exposed to either control condition or early-life stress. A, In the Y-maze test, all groups of animals spent more time exploring the novel arm versus the known ones. However, stressed wild-type mice performed significantly worse than wild-type controls, while stressed CRF₁-CKO mice displayed performance comparable to that of the controls. B, In the Morris water maze test, stressed wild-type mice took significantly longer to locate the hidden platform in the first spatial training day, indicating impaired acquisition of spatial information. In contrast, stressed CRF₁-CKO mice spent similar time to reach the platform compared with the controls. C, D, Spatial learning and memory in adult wild-type and CRF-COE mice. C, In the Y-maze test, wild-type mice showed preference to the novel arm, whereas CRF-COE mice visited the novel and familiar arms similarly. D, In the Morris water maze test, CRF-COE mice exhibited profound spatial learning impairments in the first two spatial training days and reduced cognitive flexibility in the reversal learning session. CT, Control; ES, early-life stress; KO, CRF₁-CKO; OE, CRF-COE. *p < 0.05, **p < 0.01 versus control wild-type group. ^#p < 0.05, ^##p < 0.01, ^###p < 0.001 versus respective novel arm. n = 10–20 mice per group.