Effects Of Fluoxetine On Signaling Transduction Pathway Of ERK1/2-NFκB And Serum S100B Levels In Depressed Model Rats

ObjectiveThe aims are to explore the effects of fluoxetine on special learning and memory and serum S100B levels in depressed model rats, to explore the effects of fluoxetine on the levels and activities of ERK1/2and NFκB in hippocampus and frontal cortex of depressed model rats in various treatment time.MethodsAdult male SD rats were used as experimental subjects. They were divided into six groups randomly according random digits table:control group (A), depressed model group (B), group of depressed model treated with single dose of fluoxetine for one day (C), group of depressed model treated with fluoxetine for one week (D), group of depressed model treated with fluoxetine for two weeks (E) and group of depressed model treated with fluoxetine for four weeks (F), ten rats in each group. Except control group, others were subjected to forced-swimming for four weeks,15min a day. Fluoxetine (10mg/kg)was given intragastric administration to group C-F before swimming everyday. Morris water maze (MWM) was used to measure the spatial learning and memory of rats. ELISA was used to determine the levels of serum S10OB.Adult male Sprague-Dawley rats were used as experimental subjects.They were divided into six groups:control group A, depressed model group B, group of depressed model+fluoxetine once C, group of depressed model+fluoxetine for one week D, group of depressed model+fluoxetine for two weeks E and group of depressed model+fluoxetine for four weeks F, with10rats in each group.The depressed model was made by forced swimming for4weeks. Fluoxetine (10mg/kg) was intragastricly administrated to group C, D, E,F everyday before swimming, with the treatment duration of one day, one week, two weeks and four weeks respectively.Western blot was used to determine the levels ERK1/2and NFkB in hippocampus and frontal cortex.Results1.In the hiding platform test of MWM, there was significant longer of escape latency (EL) in B group than that in A group (P<0.05). And the EL in all groups treated with fluoxetine became shorter with the prolonging of treatment. In the probe test, there were significant longer time in target quadrant in D、E、F than in other quadrant (F=5.162, P<0.01). The levels of serum S100B were lower in E, F groups[E (0.91±0.23) ng/ml, F (0.85±0.21) ng/ml] than that in B group[B (1.26±0.61) ng/ml, P<0.05].2.(1)The hippocampus and frontal cortex levels of phospho-ERK1/2in group B, group C and group D were significantly lower than that in group A (p<0.01), and there were no significant differences in the phospho-ERK1/2levels in group E and group F as compared to group A (P>0.05). There was no significant difference of the level of t-ERK1/2between control group and any other group (P>0.05).(2) The hippocampus and frontal cortex levels of phospho-NFκB in group B, group C and group D were significantly lower than that in group A (p<0.01), and there were no significant differences in the phospho-NFκB levels in group E and group F as compared to group A (P>0.05).There was no significant difference of the level of t-NFκB between control group and any other group (P>0.05).Conclusions1.Chronic administration of fluoxetine could improve the impairment of spatial learning and memory and reverse the increase of S100B levels in serum of depressed model rats.2.Chronic forced-swimming stress could inhibit ERK1/2and NFκB phosphorylation in hippocampus and frontal cortex of rats, which could be reversed by chronic administration of fluoxetine.