Objective:To investigate the changes of spontaneous and cognitive behavior,and cholinergic M receptors in the brain of mice subjected to chronic mild stress (CMS),and to determine the effect of Ning Shen Ling Granule (宁神灵冲剂,NSL) and dehydroepiandrosterone (DHEA) on them.Methods:CMS model mice were established by applying stress every day for 3 consecutive weeks with 7 kinds of unforeseeable stress sources,and they were medicated for 1 week beginning at the 3rd week of modeling.The changes in behavior were determined by Morris Water Maze and spontaneous movement test,and M-receptor binding activity in cerebral cortex,hippocampus and hypothalamus were measured by radioactive ligand assay with 3H-QNB.Results:(1)The spontaneous movement in CMS model mice was significantly reduced,with the latency for searching platform in Morris Water Maze obviously prolonged (P＜0.01),and these abnormal changes in behavior were improved in those treated with NSL and DHEA.(2)The binding ability of M-receptor in cerebral cortex and hippocampus of CMS mice was significantly decreased as compared with those in the control group (P＜0.05),but could be restored to the normal level after intervention with NSL or DHEA.Conclusion:The decline of spontaneous movement and spatial learning and memory ability could be induced in animals by chronic mild stress,and that may be related to the low activity of central cholinergic M-receptors.Both NSL and DHEA could effectively alleviate the above-mentioned changes.