國家衛生研究院 NHRI:Item 3990099045/14553
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    题名: L-4-Fluorophenylglycine produces antidepressant-like effects and enhances resilience to stress in mice
    作者: Sung, CW;Chang, WT;Chan, MH;Kuo, TH;Chen, HH
    贡献者: Center for Neuropsychiatric Research
    摘要: D-serine has attracted increasing attention for its possible role in depression. L-4-Fluorophenylglycine (L-4FPG), an inhibitor of the neutral amino acid transporter ASCT1/2, has been shown to regulate extracellular D-serine levels. The present study aimed to explore the potential antidepressant effects of L-4FPG. First, the acute effects of L-4FPG on the forced swimming test, elevated plus maze test, and novelty-suppressed feeding test were examined. L-4FPG showed antidepressant-like effects, which could be reversed by rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), an alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonist. The phosphorylation levels of mTOR and GluR1 in the hippocampus were also increased after L-4FPG treatment. Next, the therapeutic effects of L-4FPG were examined in a chronic social defeat stress (CSDS) model of depression. L-4FPG ameliorated depression-like behaviors in mice subjected to CSDS. Furthermore, treatment with L-4FPG prior to each social defeat stress session not only decreased defensive behaviors but also prevented CSDS-induced social avoidance and anxiety-like and depression-like behaviors. These findings suggest that L-4FPG may be useful not only in alleviating depression but also in protecting against chronic stress-related psychiatric disorders.
    日期: 2022-09-24
    關聯: Biomedicine and Pharmacotherapy. 2022 Sep 24;155:Article number 113726.
    Link to: http://dx.doi.org/10.1016/j.biopha.2022.113726
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0753-3322&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000869952200003
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85138635229
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