The Effect Of Acute Corticosterone Treatment On Neurochemistry And Neurothology Of Mice

Objective: Corticosterone(CORT)is a stress hormone and the hippocampus is a sensitive target of CORT.CORT has long been shown to modulate 5-HT system,and to alter hippocampal functions in various physiological and pathological conditions.However,CORT-elicited changes in the hippocampal 5-HT transmission and the immobility phenotype had not been fully addressed.The current study sought to explore effects of acute CORT subcutaneously injected at 10,20,40 mg/kg on the extracellular 5-HT in the hippocampus and the immobility time in male CD-1 mice.By clarifying the effects of acute CORT on neurochemistry and neurobehavioral behavior,it will lay the foundation for studying the 5-HT delivery of depression caused by chronic CORT administration.Methods: Two hundreds and four mice were used experiments.Following an injection of CORT,vehicle or saline,time course of the extracellular 5-HT in the hippocampal CA3 was determined using in vivo microdialysis.The immobility time was measured at 0,60,120,180 min in the forced swimming test(FST)and the tail suspension test(TST),respectively.The first set of experiments was neurochemistry that was measurement of the effect of CORT on 5-HT concentration in hippocampal CA3 by microdialysis.To measure the hippocampal 5-HT,dialysates were collected for 4 h at 20 min interval following a subcutaneous(s.c.)injection of saline,vehicle or 10,20,40 mg/kg CORT in a volume of 5 ml/kg.The second set of experiments was neurothology that was determination of the effect of CORT on immobility in mice by FST and TST.To obtain the immobility time in the FST and the TST,four assessments were performed at 60 min interval for each animal following a s.c.injection of saline,vehicle or 10,20,40 mg/kg CORT in a volume of 5 ml/kg.The third set of experiments was to run Pearson analyses to detect correlations between the immobility time and the changes in the dialysate 5-HT following CORT injections.Results:1.Chromatographic separation and retention timeThe 5-HT in the standard and dialysate samples were well separated and the 5-HT retention time was 15.2 min.2.Probe placementAll mice were detected with(70-90%)of the active membrane placed in the hippocampal CA3.3.The role of acute CORT in neurochemistryThe organic solvents had no effect on the 5-HT concentration in hippocampal CA3.CORT dose-dependently increased the concentration of 5-HT in CA3.Three doses of CORT increased the level of 5-HT in the dialysate,the magnitude of the increase varied with different doses,and the higher the dose of CORT,the greater the increase detected in the dialysate 5-HT reaction with the peak level detected at 120 min for the three doses of CORT injections.4.The role of acute CORT in neurobehavioralThe organic solvent had no effect on the resting time of the mice.CORT dosedependently decreased the immobility time in the FST and the TST.Prior to injections,the basal immobility times were found no differences across four groups(10,20,40 mg/kg CORT and vehicle).Following injections,CORT significantly decreased the immobility time at the 120 min,the magnitudes of the decreases were dose-related.Three doses of CORT decreased the immobility time of the FST and the TST,the magnitude of the decrease varied with different doses.And the higher the injection dose of CORT,the greater the decrease detected in immobility time.5.Correlations of the immobility times with the peak increases in the dialysate 5-HTThe immobility time was significantly correlated with the peak increases in the hippocampal 5-HT across the three doses of CORT.The correlations were negatively detected,i.e.the higher the peak increase in the dialysate 5-HT in the hippocampal CA3,the shorter the immobility time elicited behaviorally.Conclusion:The results showed that the peak increase in the dialysate 5-HT and the decrease in the immobility time were both obtained at the 120 min following the acute CORT injection.Furthermore,a negative correlation was detected between the immobility time and the peak increase in the dialysate 5-HT.Our results indicated that acute CORT injection elicits antidepressant-like actions on the hippocampal 5-HT and the immobility time.The study can conclude that the decrease of immobility time can be regulated by an increase in hippocampal 5-HT levels,and suggested that hippocampal 5-HT responses may be one of the neurochemical bases for the immobility phenotype following CORT injection.