Epigenetic induction of melatonin MT1 receptors by valproate: Neurotherapeutic implications

We have reported that the anticonvulsant/mood stabilizer and histone deacetylase (HDAC) inhibitor valproate (VPA) induces expression of melatonin receptors both in vitro and in vivo, but the mechanisms involved were not known. Here we show that pharmacological inhibition of CREB, PKC, PI3K, or GSK3β signaling pathways, which are known targets for VPA, do not prevent its upregulation of melatonin MT₁ receptors in rat C6 glioma cells. M344, an …