Although further studies will be required to examine the role of IGF-1 release within the mPFC in the antidepressant-like effects of ketamine using chronic stress models of depression, including chronic unpredictable stress (CUS) and chronic social defeat stress models [8, 32], to our knowledge, this is the first study to suggest that IGF-1 release in the mPFC mediates the antidepressant-like actions of ketamine. This evidence concerns the gene IGF1 and major depressive disorder.