| Objective:To observe the change of dopamine(DA)levels in hippocampal dentate gyrus(DG)during spatial learning and memory processes in a rat model of chronic unpredictable stress(CUS),and preliminarily investigate its possible mechanism.Methods:12-month-old SD rats were randomly divided into control group and CUS group.The CUS rat model was prepared as follows:rat received one stimulus randomly every day,and the same stimulus appeared discontinuously,last for 32 days.The levels of epinephrine(E)and corticosterone(CORT)in serum were measured by enzyme-linked immunosorbent assay(ELISA),and the spatial learning and memory abilities of rats were measured by Morris water maze(MWM).The levels of DA in the DG region were measured by brain microdialysis and high performance liquid chromatography(HPLC).The amplitude of field excitatory postsynaptic potential(fEPSP)in DG region was detected by electrophysiological technique.The expression of D1-like receptor(D1R)and PKA-CREB-BDNF pathway protein were detected by immunohistochemical staining or Western blot(WB).Results:(1)The levels of stress hormones(including E and CORT)in serum of the rats in CUS group were significantly higher than control group(P<0.05,respectively).(2)In the place navigation trial of MWM test,the mean escape latency and mean swimming distance in CUS rats were significantly longer than the control group(P<0.05,respectively).There was no significant difference in swimming speed between the two groups(P>0.05).In the MWM spatial probe trial,the number of platform crossing in CUS rats was significantly less than the control group(P<0.05).(3)On the 3rd day of MWM test,the fEPSP amplitude in the hippocampal DG was significantly increased in control group(P<0.05),while it was not changed in CUS group,and there are significant difference between the two groups(P<0.05).(4)During the MWM test,the DA levels in the hippocampal DG were gradually increased and then return to the basal levels in both groups,however,compared with control group,the DA levels in the DG on the 1 st-3rd days of MWM test were significantly increased in CUS group(P<0.05,respectively).(5)The expression levels of D1R-positive neurons and proteins in the hippocampal DG of CUS rats were significantly higher than control group(P<0.05).(6)The expression levels of p-PKA,p-CREB and BDNF in hippocampal DG region in CUS rats were significantly lower than control group(P<0.05,respectively).Conclusion:Chronic unpredictable stress impairs spatial learning and memory of rats by inhibiting LD-LTP formation in the hippocampal DG which may be related to the over-activation of DA-D1R system in the DG. |
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