Two studies in adult rats [50,51] treated repeatedly with intraperitoneal injections of fluoxetine for 15 days showed neuroplastic changes in the medial prefrontal cortex, a brain region involved in the pathogenesis of depression and in the antidepressant action of Fluoxetine [73,74], likely due to both downregulation of Kir4.1 and upregulation of BDNF signaling. This evidence concerns the gene BDNF and depressive disorder.