PDE4A and Anxiety: We discover that MEKi are highly effective anxiolytics in zebrafish, and that the mechanism of PDE4 blockade/cAMP activation induced anxiety is via stimulation of the RAS-MAPK signaling pathway. cAMP-MAPK signaling crosstalk in anxiety has not been previously reported, and is significant because it reveals that targeting the crosstalk MAPK signaling pathway offers a potent alternative therapeutic strategy for anxiety.