Acute Treatment with a Novel TRPC4/C5 Channel Inhibitor Produces Antidepressant and Anxiolytic-Like Effects in Mice
Yang, Li-Ping; Jiang, Fang-Jie; Wu, Gui-Sheng; Deng, Ke; Wen, Meng; Zhou, Xiaoju; Hong, Xuechuan; Zhu, Michael X.; Luo, Huai-Rong
2015-08-28
Source PublicationPLOS ONE
Volume10Issue:8
AbstractTransient receptor potential canonical (TRPC) channels are widely expressed in brain and involved in various aspects of brain function. Both TRPC4 and TRPC5 have been implicated in innate fear function, which represents a key response to environmental stress. However, to what extent the TRPC4/C5 channels are involved in psychiatric disorders remains unexplored. Here, we tested the antidepressant and anxiolytic-like effects of a newly identified TRPC4/C5 inhibitor, M084. We show that a single intraperitoneal administration of M084 at 10 mg/kg body weight to C57BL/6 male mice significantly shortened the immobility time in forced swim test and tail suspension test within as short as 2 hours. The M084-treated mice spent more time exploring in illuminated and open areas in light/dark transition test and elevated plus maze test. In mice subjected to chronic unpredictable stress, M084 treatment reversed the enhanced immobility time in forced swim test and decreased the latency to feed in novelty suppressed feeding test. The treatment of M084 increased BDNF expression in both mRNA and protein levels, as well as phosphorylation levels of AKT and ERK, in prefrontal cortex. Our results indicate that M084 exerts rapid antidepressant and anxiolytic-like effects at least in part by acting on BDNF and its downstream signaling. We propose M084 as a lead compound for further druggability research.
DOI10.1371/journal.pone.0136255
Indexed BySCI
Language英语
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000360299100067
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Cited Times:14[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/25120
Collection植物化学与西部植物资源持续利用国家重点实验室
Recommended Citation
GB/T 7714
Yang, Li-Ping,Jiang, Fang-Jie,Wu, Gui-Sheng,et al. Acute Treatment with a Novel TRPC4/C5 Channel Inhibitor Produces Antidepressant and Anxiolytic-Like Effects in Mice[J]. PLOS ONE,2015,10(8).
APA Yang, Li-Ping.,Jiang, Fang-Jie.,Wu, Gui-Sheng.,Deng, Ke.,Wen, Meng.,...&Luo, Huai-Rong.(2015).Acute Treatment with a Novel TRPC4/C5 Channel Inhibitor Produces Antidepressant and Anxiolytic-Like Effects in Mice.PLOS ONE,10(8).
MLA Yang, Li-Ping,et al."Acute Treatment with a Novel TRPC4/C5 Channel Inhibitor Produces Antidepressant and Anxiolytic-Like Effects in Mice".PLOS ONE 10.8(2015).
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