Abstract: ObjectiveTo explore effects of exercise on depressive-like behavior and the phosphorylation level of extracellular signal-regulated protein kinase(ERK)-cAMP response element binding protein(CREB) signal pathway in different cerebral regions of rats under chronic unpredictable mild stress(CUMS).MethodsForty male Sprague Dawley rats were randomly divided into 4 groups:control group,stress group,exercise plus stress group,and exercise group.The rat model of depression was made by the method of chronic unpredictable mild stress.Exercise model was established with voluntary wheel running.The open field test and sucrose preference test was utilized to determine the depressive-like behavior.Phosphorylated ERK and CREB in the frontal cortex and hippocampus were examined with immunohistochemistry.ResultsCompared with the rats of control group,chronic-stressed rats showed significantly decreased number of crossing square(20.4?11.67),times of rearing(5.4?2.36) and sucrose consumption(8.13?2.56 g,P<0.01).The p-ERK and p-CREB expressions in hippocampus(6.15?2.86,2.89?0.51) and frontal cortex(12.43?5.14,2.34?0.53) were also significantly decreased in stress group(P<0.01).Compared with stress group,exercise significantly diminished the number of crossing square,times of rearing,and body weight of the rats(48.2?22.66,13.1?3.06,17.02?4.13 g) induced by chronic stress and increased the levels of p-ERK and p-CREB in hippocampus(14.95?3.54,4.47?0.45) and frontal cortex(23.57?4.76,3.87?0.44)(P<0.05 for all).Compared with those in control group,the phosphorylation levels of ERK and CREB in the two cerebral regions(23.76?4.11,32.64?5.37,6.73?0.55,5.79?0.51) were higher in exercise group(P<0.05 for all).ConclusionExercise has certain antidepressant behavior effect,and its molecular mechanism may be associated with up-regulation of phosphorylation levels of ERK-CREB signaling pathway in brain.