Changes In Corticosterone-elicited Hippocampal Extracellular 5-HT Concentration In Depressive State

Objective: Depression is a serious neuropsychiatric disorder.The incidence rate is increasing year by year,but its pathogenesis is still unclear.The monoamine neurotransmitter serotonin(5-HT)is thought to play a leading role in the pathogenesis of depression.Glucocorticoid(GC),human cortisol,rodent corticosterone(CORT),is a terminal hormone of hypothalamic pituitary adrenal(HPA),which can regulate the 5-HT nervous system and affect the transmission of 5-HT.It has been shown that CORT can increase the concentration of 5-HT in hippocampal CA3 in a dose-dependent manner under physiological state,and the higher the dose,the greater the magnitude of the enhancement.The purpose of this experiment is to discuss the changes of 5-HT concentration in hippocampus caused by different doses of CORT injections in depressive state,and to lay a foundation for the study of the effect of CORT administration on 5-HT concentration in hippocampus during antidepressant therapy.Methods: The first part of the experiment was a behavioral experiment.CORT was administered for 3 weeks to establish a mouse model of depression.The immobility time measured by forced swimming test(FST)and tail suspension test(TST),physical state score,and body weight were used as the evaluation criteria to determine whether the mice established a depressive state.The second part of the experiment was a microdialysis experiment.According to the evaluation standard of behavioral experiment,the mice can be divided into three state groups: physiological state group,depressive state group and the control group.Then,three groups of mice were injected with three different doses of CORT,and the dynamic change of 5-HT concentration in the hippocampal CA3 area of mice was detected using in vivo microdialysis technology.Results: After 3 weeks of chronic CORT administration,a mouse depression model was successfully created.The immobility time of FST and TST in depressive mice was significantly prolonged,the physical state worsened and weight growth stopped.Compared with the physiological state group,the basal concentration of dialysate 5-HT was significantly reduced in depressive state group,while the basal concentration of dialysate 5-HT was not changed in the control group.In physiological state group and the control group,CORT dose dependently increased the 5-HT concentration in hippocampal CA3,while in depressive state group,CORT induced the increase of 5-HT in hippocampus disappeared.Conclusion: The study found that only in physiological state group and the control group,CORT dose dependently increased 5-HT in the hippocampal CA3,and the 5-HT basal concentration in the dialysate decreased significantly in depressive state compared to the physiological state group.Therefore,the decrease of extracellular 5-HT in the hippocampal CA3 and the disappearance of the increased 5-HT concentration induced by acute CORT administration may be the core characteristics of depression.