Objective To explore the rapid antidepressant potential and the underlying mechanism of Chaihu Shugan San(CSS)in female mice.Methods Liquid chromatography mass spectrometry(LC-MS)/MS was used to determine the content ...Objective To explore the rapid antidepressant potential and the underlying mechanism of Chaihu Shugan San(CSS)in female mice.Methods Liquid chromatography mass spectrometry(LC-MS)/MS was used to determine the content of main components in CSS to determine its stability.Female C57BL/6J mice were randomly divided into 4 groups,including control(saline),vehicle(saline),CSS(4 g/kg)and ketamine(30 mg/kg)groups.Mice were subjected to irregular stress stimulation for 4 weeks to establish the chronic mild stress(CMS)model,then received a single administration of drugs.Two hours later,the behavioral tests were performed,including open field test,tail suspension test(TST),forced swimming test(FST),novelty suppression feeding test(NSF),and sucrose preference test(SPT).Western blot analysis was used to detect the expression levels of N-methyl-D-aspartate receptor(NMDA)subtypes[N-methyl-D-aspartate receptor 1(NR1),NR2A,NR2B],synaptic proteins[synapsin1 and post synaptic density protein 95(PSD95)],and brain-derived neurotrophic factor(BDNF).Moreover,the rapid antidepressant effect of CSS was tested by pharmacological technologies and optogenetic interventions that activated glutamate receptors,NMDA.Results Compared with the vehicle group,a single administration of CSS(4 g/kg)reversed all behavioral defects in TST,FST,SPT and NSF caused by CMS(P<0.05 or P<0.01).CSS also significantly decreased the expressions of NMDA subtypes(NR1,NR2A,NR2B)at 2 h in hippocampus of mice(all P<0.01).In addition,similar to ketamine,CSS increased levels of synaptic proteins and BDNF(P<0.05 or P<0.01).Furthermore,the rapid antidepressant effects of CSS were blocked by transient activation of NMDA receptors in the hippocampus(all P<0.01).Conclusion Rapid antidepressant effects of CSS by improving behavioral deficits in female CMS mice depended on rapid suppression of NMDA receptors and activation of synaptic proteins.展开更多
基金Supported by the National Natural Science Foundation of China(No.82174107,82304898)Jiangsu Provincial Administration of Traditional Chinese Medicine Fund(No.YB2020014)the Priority Academic Program Development of Jiangsu Higher Education Institutions(No.035062005001)。
文摘Objective To explore the rapid antidepressant potential and the underlying mechanism of Chaihu Shugan San(CSS)in female mice.Methods Liquid chromatography mass spectrometry(LC-MS)/MS was used to determine the content of main components in CSS to determine its stability.Female C57BL/6J mice were randomly divided into 4 groups,including control(saline),vehicle(saline),CSS(4 g/kg)and ketamine(30 mg/kg)groups.Mice were subjected to irregular stress stimulation for 4 weeks to establish the chronic mild stress(CMS)model,then received a single administration of drugs.Two hours later,the behavioral tests were performed,including open field test,tail suspension test(TST),forced swimming test(FST),novelty suppression feeding test(NSF),and sucrose preference test(SPT).Western blot analysis was used to detect the expression levels of N-methyl-D-aspartate receptor(NMDA)subtypes[N-methyl-D-aspartate receptor 1(NR1),NR2A,NR2B],synaptic proteins[synapsin1 and post synaptic density protein 95(PSD95)],and brain-derived neurotrophic factor(BDNF).Moreover,the rapid antidepressant effect of CSS was tested by pharmacological technologies and optogenetic interventions that activated glutamate receptors,NMDA.Results Compared with the vehicle group,a single administration of CSS(4 g/kg)reversed all behavioral defects in TST,FST,SPT and NSF caused by CMS(P<0.05 or P<0.01).CSS also significantly decreased the expressions of NMDA subtypes(NR1,NR2A,NR2B)at 2 h in hippocampus of mice(all P<0.01).In addition,similar to ketamine,CSS increased levels of synaptic proteins and BDNF(P<0.05 or P<0.01).Furthermore,the rapid antidepressant effects of CSS were blocked by transient activation of NMDA receptors in the hippocampus(all P<0.01).Conclusion Rapid antidepressant effects of CSS by improving behavioral deficits in female CMS mice depended on rapid suppression of NMDA receptors and activation of synaptic proteins.
