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Significance Depression is a serious disease afflicting an increasing number of people, including adolescents. Animal studies indicate that the neuropeptide galanin and its three receptors, GalR1 to 3, are involved in depression-like behavior, evidenced by increased GalR1 transcript levels in the ventral periaqueductal gray of “depressed” rats. Here, we show coexistence of Scratch2 and GalR1, identifying a possible mechanism underlying control of GalR1 expression in this region: the transcription factor Scratch2 lowers, via binding to an E-box in theGalR1 promoter, expression of the GalR1 receptor. This may represent a further role for Scratch2, earlier associated with embryonic development, cell migration, and neurogenesis. Because GalR1 seems involved in major depression, we discuss whether or not Scratch2 also may play a role in the human disease.

Involvement of Scratch2 in GalR1-mediated depression-like behaviors in the rat ventral periaqueductal gray