四氢孕酮抗焦虑效应及潜在机制OA

OBJECTIVE To investigate the anxiolytic effects of allopregnanolone(Allo)in stress model mice and explore its potential mechanisms.METHODS Male C57BL/6 mice were randomly assigned to the control group,model group,model+Allo 5,10 and 20 mg·kg-1 groups.An anxiety model was induced by acute restraint stress(ARS),and the anxiolytic behavioral changes of Allo were evalu-ated using the open field test(OFT)and elevated plus maze test(EPMT).Following the multi-dose behavioral assessment,the effective dose of Allo 10 mg·kg-1 was selected for mechanistic investiga-tion.Experimental groups included the control group,model group,and model+Allo 10 mg·kg-1 group.In vivo fiber photometry was employed to observe dynamic changes in neuronal activity in the medial prefrontal cortex(mPFC)and hippocampus.Golgi staining was used to examine the effects of Allo on the density and complexity of dendritic spines of neurons in the mPFC and hippocampus.ELISA was performed to measure the levels of brain-derived neurotrophic factor(BDNF),glutamate ionotropic receptor AMPA type subunit 1(GluA1),and synapsin 1(SYN1)in the mPFC and hippocampus.RESULTS Compared with the control group,there was a significant decrease in the percentage of distance traveled and time spent in the center area in the OFT,as well as a significant reduction in the number of entries into the open arms in the EPMT in the model group.A single administration of Allo 10 mg·kg-1 significantly reversed these behavioral alterations compared to the model group.Fiber photom-etry recordings revealed a significant reduction in calcium signal activity in both the mPFC and hippo-campus of model mice,which was also significantly reversed by a single dose of Allo 10 mg·kg-1.Golgi staining results suggested that Allo 10 mg·kg-1 significantly counteracted the ARS-induced decrease in dendritic spine density and complexity in the mPFC and hippocampus.ELISA results indicated that Allo 10 mg·kg-1 significantly reversed the ARS-induced reductions in the levels of BDNF,GluA1,and SYN1 in both the mPFC and hippocampus.CONCLUSION Allo can significantly alleviate ARS-induced anxiety-like behaviors,and such effects may be closely associated with the restoration of neuronal activity in the mPFC and hippocampus,as well as the modulation of related synaptic plasticity in the brain.