In order to provide direct evidence of the potential role of the ERK pathway in depression, mice were infused with U0126 infusion into the dorsal hippocampus (dHP) and prefrontal cortex (mPFC), after which the depressive symptoms including lack of pleasure and anxiety-like behavior appear and the p-CREB levels of dHP and mPFC decreased [49]. This evidence concerns the gene CREB1 and depressive disorder.