Figure 3. Hippocampus-dependent learning and memory were preserved in early-life stress rats treated systemically with a blocker of CRF1, NBI30775, during P10–P17. A, During the first 2 training days, all groups successfully learned to find the hidden platform (effect of trial: F(11,539) = 7.73, p < 0.001). Early-life stress impaired acquisition of the water maze (effect of stress condition: F(1,49) = 11.09, p < 0.005), and CRF1 blocker treatment improved performance regardless of stress exposure (F(1,49) = 5.7, p < 0.05). Compared to CTL middle-aged rats (n = 20), age-matched CES rats (n = 13) required more time on the last trial of each water maze training day (trials 6 and 12) to find a hidden platform (*p < 0.05, CES vs CTL). At the end of training (trial 12), this deficit was completely abolished in the stressed group that received CRF1 antagonist (CES+ANT; n = 8; #p < 0.05, vs CES; p > 0.05, vs CTL). B, On day 3 of the water maze, the platform was moved to a new quadrant and rats relied on strategically placed spatial cues to learn the new platform location. Untreated control rats, as well as control (CTL+ANT; n = 4) and early-stressed groups treated with a CRF1 blocker, successfully learned the task, whereas untreated stressed rats had significantly higher escape latencies (*p < 0.05, CES vs all other groups). Analysis of the last trial of the reversal procedure indicated that by the end of testing, CES rats had not learned the new platform location as well as controls (t(40) = 3.26, p < 0.05), and CRF1 antagonist treatment reversed this deficit (CES vs CES+ANT: t(23) = 3.34, p < 0.005; CES+ANT vs CTL: t(31) = 1.33, p = 0.19). C, On day 1 of the object recognition task, exploration times of both objects were similar among the four experimental groups. D, On day 2, preferential exploration of the novel object (apparent from the increased ratio of time spent with novel versus the familiar objects) was observed in untreated control rats (ratio: 2.14), as well as CRF1 blocker-treated controls (ratio: 1.75). The cohort of middle-aged CES rats given the CRF1 receptor blocker also discriminated between the novel and familiar objects (ratio: 1.84), evidenced by a significantly higher mean exploration ratio compared to untreated CES rats (ratio: 0.99; p < 0.0001) (*p < 0.05, CES vs all other groups). Error bars indicate SEM.