中国药理学与毒理学杂志2026，Vol.40Issue(2)：94-103,10.DOI:10.3867/j.issn.1000-3002.2026.08784
四氢孕酮抗焦虑效应及潜在机制
Anxiolytic effects and mechanisms of allopregnanolone
摘要
Abstract
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.关键词
四氢孕酮/焦虑/急性束缚应激/突触可塑性/内侧前额叶皮质/海马Key words
allopregnanolone/anxiety/acute restraint stress/synaptic plasticity/mPFC/hippocampus分类
医药卫生引用本文复制引用
张慧颖,赵佳宁,毕鹏威,张爽,李云峰,张阔,尹勇玉,张黎明..四氢孕酮抗焦虑效应及潜在机制[J].中国药理学与毒理学杂志,2026,40(2):94-103,10.基金项目
脑科学与类脑研究国家科技重大专项(2021ZD-0202000) "Brain Science and Brain-Inspired Research"National Science and Technology Major Project(2021ZD-0202000) （2021ZD-0202000）
