Effects Of Chronic Restraint Stress On Excitatory Amino Acids Levels In The Dentate Gyrus Of Aged Rats

Objective:To observe the changes of excitatory amino acids level in the hippocampal dentate gyrus(DG)during spatial learning and memory in aged rats under chronic restraint stress(CRS)condition,and to investigate the neurochemical mechanism of CRS affecting the spatial learning and memory.Methods:18 month old rats were subjected to restraint stimulation 2 hours every day last for 30 days to prepare a chronic restrain stress(CRS)model.The levels of corticosterone(CORT)and epinephrine(EPI)in serum were measured by ELISA assay,and the spatial learning and memory abilities of rats were assessed by Morris water maze(MWM).The extracellular concentrations of excitatory amino acids,including aspirate(Asp)and glutamate(Glu),in the DG were determined by in vivo microdialysis and HPLC.Results:(1)The levels of CORT and EPI in serum of the rats in CRS group were significantly higher than those in the control group(P<0.05,respectively);moreover,the stress hormone level of male CRS group was significantly higher than that female CRS group.(2)Contrasted to the control group,the concentration of Glu in the DG was significantly decreased in male CRS group(P<0.05),despite the concentration of Asp was not changed(P>0.05);the concentrations of Asp and Glu in the DG were not significantly changed in female CRS group(P>0.05,respectively),and there was no prevalent differences in the content of Glu and Asp in the DG between male and female(all P>0.05).(3)During place navigation trial of MWM test,compared with the control group,the escape latencies on the 2nd-4nd days were significantly increased in male CRS group(P<0.05,respectively),but there was no significant change in the escape latency in female CRS group(P>0.05,respectively),and there was no significant difference between male and female.(4)In the spatial prove trial of MWM test,compared with the control group,the percentage of time spent in target quadrant were markedly decreased in male CRS group(P<0.05),and significantly lower than the female CRS rats(P<0.05),whereas the percentage of time spent in target quadrant was not markedly changed in female CRS group(P>0.05).(5)Compared with the control group,the Asp level of the DG in male CRS group was significantly reduced on the 3rd day in MWM test(P<0.05),and significantly lower than the female CRS rats(P<0.05),while there was no significant difference in Asp level between the control and female CRS group(P>0.05).(6)In place navigation trial of MWM test,the Glu levels of the DG in both male and female CRS groups were markedly increased(P<0.05,respectively),and there were no significant difference in Glu level contrasted to the control group(P>0.05,respectively),and there also was no significant difference between male and female.Conclusion:Chronic restraint stress impairs spatial learning and memory in male aged rats,which may be related to decrease of excitatory amino acids level in hippocampal DG region.