抗焦虑药
齿状回
焦虑
药理学
高架加迷宫
海马结构
医学
氟西汀
焦虑症
精神科
内科学
受体
血清素
作者
Nicolás Panayotis,Philip A. Freund,Letizia Marvaldi,Tali Shalit,Alexander Brandis,Tevie Mehlman,Michael Tsoory,Mike Fainzilber
标识
DOI:10.1016/j.xcrm.2021.100281
摘要
Anxiety and stress-related conditions represent a significant health burden in modern society. Unfortunately, most anxiolytic drugs are prone to side effects, limiting their long-term usage. Here, we employ a bioinformatics screen to identify drugs for repurposing as anxiolytics. Comparison of drug-induced gene-expression profiles with the hippocampal transcriptome of an importin α5 mutant mouse model with reduced anxiety identifies the hypocholesterolemic agent β-sitosterol as a promising candidate. β-sitosterol activity is validated by both intraperitoneal and oral application in mice, revealing it as the only clear anxiolytic from five closely related phytosterols. β-sitosterol injection reduces the effects of restraint stress, contextual fear memory, and c-Fos activation in the prefrontal cortex and dentate gyrus. Moreover, synergistic anxiolysis is observed when combining sub-efficacious doses of β-sitosterol with the SSRI fluoxetine. These preclinical findings support further development of β-sitosterol, either as a standalone anxiolytic or in combination with low-dose SSRIs.
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