Effect of fluoxetine on the depression-like behavior and mitogen-activated protein kinase-p38 signaling pathway in depression rats / 新乡医学院学报

ABSTRACT

Objective To investigate the effect of fluoxetine on the depression-like behavior and the expression of mitogen-activated protein kinase phosphatase-1 (MKP-1),phosphorylated p38 and p38 in hippocampus of rats with depression,in order to provide clues for the molecular pathological mechanism of depression.Methods Forty Sprague Dawley rats were randomly divided into normal group,depression group,normal saline group and fluoxetine group,with ten rats in each group.The rats in the depression group,normal saline group and fluoxetine group were treated with chronic unpredictable mild stress (CUMS) for eight weeks to prepare the depression models.The rats in the normal saline group and fluoxetine group were treated with normal saline and fluoxetine by intragastric administration respectively from the fifth to eighth week,but the rats in the normal group did not give CUMS and any intervention.The behavior changes of rats in the four groups were evaluated at the time points of before modeling,after modeling and postintervention.The hippocampal tissues of rats were taken after the last the last behavioral evaluations.The expression of MKP-1,p-p38 and p38 protein in hippocampus was detected by Western blot;and the ratio of the expression of p-p38 to p38 protein (p-p38/p38) was calculated.Results There was no significant difference in the behavioral indexes of rats among the four groups (P ＞ 0.05).Compared with pre-modeling,the sucrose preference index decreased,the horizontal movement distance and vertical frequency decreased in the open field test,and the inactivity time of rats in forced swimming test increased in the depression group,normal saline group and fluoxetine group,the differences were statistically significant (P ＜ 0.05).There was no significant difference in the behavioral indexes of rats among the depression group,normal saline group and fluoxetine group (P ＞ 0.05).Compared with the normal group,the sucrose preference index decreased,the horizontal movement distance and vertical frequency of rats in open field test decreased,and the inactivity time of rats in forced swimming test increased in the depression group,normal saline group and fluoxetine group after modeling,the differences were statistically significant(P ＜0.05).Compared with the depression group and normal saline group,the sucrose preference index of rats increased,the horizontal movement distance and vertical frequency of rats in open field test increased,and the inactivity time of rats in forced swimming test shortened in fluoxetine group,the differences were statistically significant (P ＜ 0.05).The expression of MKP-1 in the hippocampus of rats in the depression group and the normal saline group was significantly higher than that in the normal group (P ＜ 0.05).The expression of MKP-1 in the hippocampus of rats in the fluoxetine group was significantly lower than that in the depression group and normal saline group (P ＜ 0.05).There was no significant difference in the expression of MKP-1 in the hippocampus of rats between the depression group and the normal saline group (P ＞ 0.05).There was no significant difference in the expression of MKP-1 in the hippocampus of rats between the fluoxetine group and normal group(P ＞ 0.05).There was no significant difference in the expression of p-p38 and p38 protein and p-p38/p38 in the hippocampus of rats among the four groups (P ＞ 0.05).Conclusions MKP-1 may be associated with the pathogenesis of depression,and p38 may not be the signaling pathway for MKP-1 to take part in the pathogenesis of depression.Fluoxetine may play a role in the treatment of depression by down-regulating MKP-1 expression.MKP-1 may play a key role in the pathogenesis of depression.Fluoxetine may play a role in the treatment of depression by down-regulating.