| Objective To investigate the effects of propofol combined with electroconvulsive therapy(ECT)on behavior, learning ability and memory in depressed rats, and changes of expression of neuronal nitric oxide synthase (nNOS) mRNA and protein, Fos protein, as well as NOS activity and NO concentration in hippocamps of depressed rats after ECT, so as to uncover the mechanism of propofol combined with ECT effecting on the learning ability and memory in depressed rats.Methods Sixty adult male SD rats were randomly divided into five groups (n=12), control group (group C), depressed model group (group D), electroconvulsive therapy (ECT) group (group E), propofol combined with ECT group (group M)and propofol group (group P) . Group C were raised normally, and other groups were set up chronic unpredictable mild stress depressed model. Then group E and M were given ECT or propofol combined with ECT respectively for 6 times, and group P were treated with intraperitoneal injection of propofol 100 mg/kg when ECT was performed, while group D weren't treated. All rats were given open-field tests to investigate horizontal and vertical score before and after modeling and after treatment. After the last open-field tests were completed, all rats were put into Morris water maze to test escape latency and percentage of swimming distance in the platform quadrant to assess learning ability and memory function. Then all rats'hippocamps were taken to detect Fos and nNOS expression by immunohistochemical staining whose immunoreactive positive products were analyzed by image analysis system with the indicators of the cross-section area ratio and the average gray scale, expression of nNOS-mRNA by RT-PCR, and NOS activity and NO concentration with spectro-photometer. All datas were analyzed with ANOVA and nonparametric tests.Results Behavior score: In horizontal and vertical score, there were no significant differences in 3 tests in group C. After modeling and after treatment, there were no statistical differences in group D and P, both of which were lower than those before modeling. In group E and M, scores after modeling and after treatment were obviously lower than those before modeling, but those after treatment were markedly higher than those after modeling. There were no remarkable differences in all groups before modeling and among group D,E,P and M after modeling, scores of which were all lower than those in group C. After treatment, those in group D,E,P and M were all lower than group C, and scores in group E and M were notably higher than group D and P, while there were no significant differences between group D and P, group E and M. There was no notable difference of escape latency between group C and M, which was apparently shorted than group D, E and P; while that in group D and P revealed slight difference but proved to be remarkably longer than group E. The change of percentage of swimming distance in the platform quadrant was opposite to escape latency. The differences of the cross-section area ratio of positive Fos and nNOS neurons in group C, P and M respectively suggested no statistical significance, which were evidently lower than that in group D or E, while this indicator in group E was markedly higher than that in group D, and the change of average gray scale was opposite. The results of nNOS-mRNA expression relative amount, NOS activity and NO concentration were accordance with the cross-section area ratio of positive Fos neurons. P<0.05 were considered to differ significantly in results.Conclusion Propofol had no obvious effects on behavior, learning ability and memory, and ECT could improve behavior but damage learning ability and memory notably, however, propofol combined with ECT improved behavior, learning ability and memory in depressed rats. The probable mechanism of the latter effects maybe that propofol could weaken Fos protein expression and the central neurotoxicity of excessive NO induced by NOS through inhibiting the expression of nNOS-mRNA in hippocamps, both of which resulted from ECT. |
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