Effect Of CORT On 5-HT In The Hippocampal CA3 Of The Depressive-Like Mice Treated With Fluoxetine

OBJECTIVE:Based on the serotonin（5-HT）neurotransmitter hypothesis of depression,we aimed to explore the basic 5-HT concentration and dynamic changes of acute corticosterone（CORT）-induced 5-HT responses in the hippocampal CA3 subregion during the pharmacotherapy of depression using microdialysis combined with electrochemical high-performance liquid chromatography（HPLC）.METHODS:37 male C57BL/6 mice were used for the experiment.Mice were injected subcutaneously with 20 mg/kg CORT for 3 weeks to establish depression model.Depressed mice were divided into two groups from the 4^{t h} week,and were given 10mg/kg of fluoxetine（FLX）treatment or saline control for 4 week.Using behavioral indicators as the criterion to determine depressive-like state and therapeutic response to FLX in the mice.There were five behavioral states established:baseline,depressive-like group,FLX-effective group,and FLX-resistant group and saline-treated group.The microdialysis technique coupled with HPLC was used to detect the dynamic changes of5-HT in the hippocampal CA3 subregion of mice after acute CORT administration in the five different states.RESULTS:There were 44%（7 out of 16）of the mice identified as the FLX-effective,44%of the depressed mice behavioral experiments returned to the baseline state.The basal concentration of 5-HT in depressed mice can be restored to the baseline through FLX treatment.The ineffective treatment of FLX not only further exacerbated behaviorally,the basal concentration of 5-HT was lower.In the FLX-effective group,the dialysate 5-HT response to acute 20 mg/kg CORT injection was the same as the increased responses at baseline.However,there was no changes in 5-HT concentration in hippocampal CA3 subregion after acute CORT administration in the FLX-resistant group,which was the same as the saline control group.CONCLUSION:In the FLX-effective group,the basal 5-HT concentration in the hippocampal C A3 subregion of depressed mice increased back to the baseline,and the increased dialysate 5-HT in the hippocampal CA3 subregion after acute CORT administration is the same as the increase in 5-HT concentration at baseline state.These results suggested that those changes maybe the signature changes of depression.The ineffective response to FLX,a form of the treatment-resistant depression（TRD）,failed to reverse the changes detected at the depressive-like state.