Valproic acid (VPA) is widely used as an antiepileptic drug or mood stabilizer. In this study, we evaluated the effects of treatment with 2 mM VPA for 3 h on cell proliferation in the telencephalic area of zebrafish larvae using bromodeoxyuridine (BRDU) to label dividing cells. It was demonstrated that 2 mM VPA exposure for 3 h at 2 and 3 days post-fertilization (dpf) larvae decreased cell proliferation in the telencephalic area of 5 dpf larvae. The reduced cell proliferation was not restored at 10 dpf larvae. The quantitative real-time PCR (qRT-PCR) data indicated that mRNA expression levels of WNT signaling pathway-related factors such as β-catenin, LEF1, and gsk3β were altered in the zebrafish larvae treated with 2 mM VPA at 2 and 3 pdf. It was also demonstrated that 2 mM VPA exposure affected color preference of the zebrafish larvae, reducing blue color preference at 5 dpf larvae. The altered color preference was restored at 10 dpf larvae. These results suggest that VPA exposure may cause molecular, cellular, and behavioral alterations in early developmental stage of the zebrafish.
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