Acute Treatment with a Novel TRPC4/C5 Channel Inhibitor Produces Antidepressant and Anxiolytic-Like Effects in Mice

PloS One
Li-Ping YangHuai-Rong Luo

Abstract

Transient 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 an...Continue Reading

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Oct 4, 2015·Neuroscience Letters·Hong WeiAntti Pertovaara
Mar 25, 2017·The International Journal of Neuropsychopharmacology·Feng-Guo LiuChao Huang
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Methods Mentioned

BETA
pharmacotherapies

Software Mentioned

Masslynx
ARRIVE
SPSS

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