| Objective To testify the effects of ECS(electroconvulsive shock,ECS)of different times on antidepressant action and learning and memory impairment in depressed rats and the field excitatory postsynaptic potential(fEPSP)in the rat hippocampus Shaffer collateral-CA1 region and long-term potentiation(long-term potentiation,LTP).Elevating the electrical stimulus to determine ECS on the expression and function of ?-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor(AMPAR)Protein and explore the mechanism of electrical stimulus resistance of ECS and impaired learning and memory function in depressive ratsMethodsPartHealthy Sprague Dawley(SD)male rats were used to establish a depressive rats model,which was cage feeding and applied with the chronic unpredictable mild stress(CUMS).After the model was successfully established,eighty depressive rats were randomly divided into depression group(Group D)and depression plus ECS group(Group DE).The Group DE was divided into a single ECS group(Group DE1),three times of ECS groups(Group DE3),five times of ECS groups(Group DE5),and seven times of ECS groups(Group DE7)according to the total number of ECS treatments.Only rats fed the same conditions in the same period as the control group(Group C).16 rats in each group.Group D and group DE were given sham ECS(stimulation electrode clipped to the rat's ears,no electricity)and ECS treatment(120mC),respectively.The rats in each group of DE were given ECS at different total times,and the rats received only one ECS treatment per day.Sucrose preference test was used to evaluate the depression-like behavior of rats before and after ECS treatment.The Morris water maze test(MWM)was used to determine the spatial learning and memory function after ECS treatment.The basic synaptic transmission efficiency of the neural pathways in the isolated acute hippocampal slice(SC-CA1)region of each group was recorded extracellularly: field excitatory postsynaptic potential(fEPSP);long-term potentiation(LTP)was also observed by high frequency stimulation.Part ?Healthy Sprague-Dawley(SD)male Sprague-Dawley(SD)rats were selected and the depression model was established using cage feeding and CUMS.A total of 32 successfully model rats were randomly selected and divided into 5 times of ECS group(Group De5)and 7 times of ECS group(Group De7).Both groups received ECS treatment at 120 mC daily for the first 5 days.Group De7 received ECS treatment at 180 mC on days 6 and 7,while Group De5 received sham ESC treatment.Detection of GluR1 expression in hippocampus,AMPAR-mediated fEPSP and LTPResultsPart ?(1)Sucrose preference experiment: After CUMS modeling,the difference in SPP between the groups was statistically significant(F=19.33,P<0.05).Compared with group C,the SPP in depressed rats of group D and DE(DE1,DE3,DE5,DE7)decreased(P<0.05),while there was no significant difference between group D and DE(P>0.05);After ECS treatment,there was a statistically significant difference in SPP among groups(F=22.52,P<0.05).Compared with group D,SPP in Group DE5 and Group DE7 was significantly increased(P<0.05),but still lower than that in group C(P<0.05).There was no statistical difference between Group DE5 and Group DE7(P>0.05).There was no significant difference in SPP among the three groups(D,DE1,DE3)(P>0.05).(2)MWM assessment of learning and memory function: There was no significant difference in swimming speed among the rats in the MWM test(P>0.05).Compared with the Group C,the escape latency(EL)was prolonged in the Group D and Group DE depression rats.(P<0.05),the space exploration time(SET)was shortened(P<0.05);compared with group D,DE6 and DE7 extended their escape latency and shorten space exploration time(SET)(P<0.05).(3)Baseline fEPSP slope,the difference between the groups was statistically significant(F=66.127,P<0.05).Compared with group D and Group DE1,baseline fEPSP slope of DE3,DE5 and DE7 were all increased(P<0.05).There was no significant difference in baseline fEPSP slope between group D and group DE1(P>0.05).Compared with DE3 group,the baseline fEPSP slope of Group DE5 and DE7 was significantly increased(P<0.05).There was no significant difference between Group DE5 and DE7(P>0.05).(4)LTP was induced by(100Hz,200P).There was a significant difference in LTP between groups(F=43.522,P<0.05).Compared with Group C,LTP in Group D and ECT treatment groups(Group DE1,Group DE3,Group DE5,Group DE7)were significantly decreased(P<0.05),of which there was no significant difference in LTP between group D and Group DE1(P>0.05).Compared with group D,LTP in Group DE3,Group DE5 and Group DE7 were decreased significantly(P<0.05).Compared with Group DE1,LTP in group DE3,group DE5 and group DE7 were decreased significantly(P<0.05);In group comparison,LTP in Group DE5 and Group DE7 were decreased further(P<0.05).There was no significant difference in LTP between group DE5 and group DE7.Part ?Sucrose preference test: After elevating stimulus of ECS to 180 mC,group De7 was significantly higher in SPP than group De5(P<0.05);(2)MWM assessed learning and memory function: There was no significant difference in swimming speed between the two groups(P>0.05);Group De7 had prolonged escape latency(EL)than group De5(P<0.05),space exploration time(SET)was shortened(P<0.05);(3)Electrophysiological experiments: Group De7 compared with group De5 baseline fEPSP slope significantly increased and the difference was statistically significant(P<0.05);after given LTP-induced stimulation,group De7 was significantly lower than group De5(P<0.05);(4)the expression of GluR1 in De7 was higher in De5(P<0.05)?Conclusions(1)Depressive rats have electrical stimulus resistance and learning and memory function impairment(2)Under constant electrical charge,the effects of ECS on hippocampal synaptic transmission efficiency and synaptic plasticity are time-dependent and have a capping effect.(3)Metaplasticity may be a mechanism in which electricity stimulus resistance has the intrinsic link with learning and memory function impairment. |
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