Abstract: Objective To study the effect of chronic stress on spatial learning-memory and the role of membrane fluidity and free calcium concentrations(Ca²⁺i)of prefrontal cortical and hippocampal synaptosomes in mice of different age.Methods The chronic stress model of mice was induced by stimulation of multiple stressors for 21 days.The spatial learning-memory ability of mice were tested using Morris water maze task.The changes of synaptosomal membrane fluidity andCa²⁺i of prefrontal cortex(PFC)and hippocampus(HP)in mice brain were also examined.Results The escape latency and the swimming time of first quadrants in young and aged control mice were 63.62±4.38 and 38.63±3.04,and 76.46±3.32 and 36.24±2.65.Compared with the young control mice,the ability of spatial learning and memory were significantly decreased(P<0.05,P<0.01)in aged control mice.The anisotropy(r value)of membrane in PFC and HP were 0.1917±0.0015 and 0.1946±0.0012 in aged control mice,and significantly higher than those of the young control mice(P<0.01,P<0.05).TheCa²⁺i in PFC and HP were 1.263±0.050 and 1.465±0.063,and obvious increased compared with those of the young control mice(P<0.05,P<0.05).After chronic stress,the escape latency and the swimming time of first quadrants in young stress mice were 64.32±4.56 and 34.56±2.83.Compared with the control mice,the ability of spatial learning and memory of the stress mice were significantly decreased(P<0.01,P<0.05).The rvalue of membrane in PFC and HP were 0.1846±0.0008,0.1888±0.0010 in young stress mice and significantly higher than those of the control mice(P<0.001,P<0.01).The Ca²⁺i in PFC and HP were 1.368±0.135 and 1.956±0.170,with obvious increases compared to control mice(P<0.05,P<0.01). The aged stress mice had more serious changes after chronic stress.Conclusion The aging and the chronic stress cause damage of spatial learning and memory function in mice which may be related to the changes of membrane fluidity and Ca²⁺i of synaptosomes.