Abstract: AIM: To investigate the alteration of behavior, such as spontaneous movement, spatial memory ability and cholinergic M receptors in the brain of mice with chronic mild stress (CMS).And to determine whether dehydroepiandrosterone (DHEA) can reverse the cognitive impairment in this model.METHODS: Forty mice were divided into four groups:control group, CMS group, CMS + DHEA low dose (ip, DHEA 5mg·kg^-1 ·d^-1) group and CMS +DHEA high dose (ip,DHEA 20 mg·kg^-1·d^-1) group. Morris water maze procedure was used to determine the spatial memory ability and M receptor binding activity was measured with radioactivity assay by 3H-QNB.RESULTS: (1) After 3 weeks in CMS, the spontaneous movement test decreased, and the latency in Morris water maze obviously prolonged. Treating CMS mice with DHEA for 3 weeks could enhance spontaneous movement and latency declined.(2) Whereas the 3H-QNB binding ability to M receptor showed a significantly decrease in cerebral cortex and hippocampus of CMS mice (P<0.05).But decreased ability of M receptor binding was reversed by DHEA treatment in hippocampus (P<0.05).CONCLUSION: DHEA can alleviate the stress response and reverse cognitive impairment induced by CMS, and it may be concerned with the central cholinergic M receptors activity.The studies also show that the low dose of DHEA is better to the CMS model than high dose.

Key words: chronic mild stress (CMS), dehydroepiandrosterone (DHEA), central cholinergic M receptor, spontaneous movement, Morris water maze