MAS impairs hippocampus-dependent spatial memory. A, During an object location test, mice exposed to simultaneous stresses lasting 60–90 min failed to spend more time exploring the novel location compared with the familiar, as indicated by the discrimination ratio (novel vs familiar; n = 5 mice/group; t(12) = 3.23, *p < 0.01). B, Plasma CORT levels at the time of the training session, 2 h after the end of the stresses, were comparable between controls and stressed mice (n = 4 mice/group, p = 0.15). C, Comparable exploration durations between control and stressed mice during the training (10 min) and testing (5 min) phases of a novel location task (n = 8 mice/group, p > 0.05). D–F, Memory deficits provoked by multiple acute stresses persisted 1 d and 1 week later. Another cohort of stressed mice was allowed to recover for 24 h or 1 week, which was followed by training (10 min) and testing (5 min). Controls explored the object in a novel location more than the object left in the familiar location, whereas stressed mice trained 1 d or 1 week after the MAS and tested 6 h later spent almost equal time exploring either (D) (main effect of stress, F(1, 28) = 5.86, *p < 0.05). Exploration times during the training and testing phases did not distinguish between the controls and stressed animals that recovered for 24 h (E) or 1 week (F) (n = 8 mice per group; p > 0.05).