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Objective To investigate the effects of acute and chronic stress on the spatial learning-memory function in mice and its mechanism.Methods Using animal model of single-factor acute stress (foot shock) and multivariate chronic unpredictable stress (crowding, cold / hot stimulation, flat noise, hathpace, foot shock, 28 days).The ability of spatial learning and memory in mice were examined by Morris water maze task, and the expression of c-fos in the hippocampus (HP) and prefrontal cortex (PFC) were measured by irnmunohistochemical method.Results The results showed that compared with control group mice, the spatial learning and memory of acute stress group mice were significantly increased in Morris water maze, and the expression ofc-fos in the CA1, CA3 region and dentate gyrus (DG) of hippocampus and PFC were significantly increased in acute stress group mice.After chronic stress, compared with the control group mice, the spatial learning-memory function of chronic stress group mice were markedly decreased, and the expression of c-fos in the CA1, CA3, DG and PFC were remarkably reduced in chronic stress group mice.Conclusion The results suggested that acute and chronic stress causes the changes of spatial learning and memory function in mice which may be nearly related to the up-or down-regulation of c-fos expression in the HP and PFC.