Changes In The Hippocampal 5-HT System During The Pathogenesis And Treatment Of Depression In Mice

Objective: Depression is one of the most common psychiatric disorders,its underlying neural mechanisms have not been fully understood,catecholamine neurotransmitter systems,such as serotonin(5-HT),have been clearly implicated in the disease’s pathogenesis.In our study,behavioral monitoring and the no-net-flux method of microdialysis were jointly used to explore changes in the hippocampal 5-HT system during the pathogenesis and treatment of depression in mice.Methods: Seventy-seven male C57/BL mice were used.Each mouse was given corticosterone(CORT)daily for 7 weeks.The first 3 weeks of CORT treatment was aimed to establish depressive state,starting from the 4th week,mice were divided into two groups receiving fluoxetine(FLX)or saline,respectively.The immobility times obtained in the forced swimming test(FST)and the tail suspension test(TST),and the scores measured in assessing the physical state of the coat,were used to determine depressive state and therapeutic response to FLX.Body weight was also monitored across weeks.The baseline,depressive state,FLX(+),FLX(-),and saline-treated controls were the five behaviorally established states.At each state,the actual extracellular 5-HT concentration and the reuptake efficiency were determined using the no-net-flux method.Results: Depressive state was steadily established by 3-week CORT injection,and completely reversed by 4-week FLX(+)treatment.Basal dialysate 5-HT was decreased in the depressive state,and recovered by the FLX treatment.A further decrease was detected only in the FLX(-)mice.The x-intercepts and slopes obtained from the no-netflux regression were decreased in the depressive state,and normalized by the FLX treatment,that were further decreased in the FLX(-)mice Conclusion: Hippocampal 5-HT concentration was decreased in the depressive state,the 5-HT reuptake efficiency was increased in the depressive state.Both of them were restored in the FLX(+)mice,whereas not changes were observed following the saline treatment.Our results indicate that the association between the decreased extracellular 5-HT and the increased 5-HT uptake in the hippocampal 5-HT system was the core change in the depressive state.Moreover,further decrease and increase were detected in extracellular 5-HT and 5-HT uptake in the FLX(-)mice.