Antidepressant-induced cell proliferation in the SGZ is mediated by VEGF-Flk-1 signaling. Immunohistochemical visualization of BrdU was followed by confocal analysis and z-sectioning to identify newborn endothelial cells. (A) Representative coronal section through the dentate gyrus with immunoperoxidase labeled BrdU (black arrowheads). (Scale bar, 50 μm.) (B) Representative colabeled cell in the SGZ labeled expressing both BrdU (red) and the endothelial cell marker RECA (green) at 63× magnification. (Scale bar, 10 μm.) (C) Quantification of BrdU-positive cells in the SGZ of the hippocampus after chronic fluoxetine injections (14 days) compared with saline controls [F(1, 8) = 34.129, P < 0.01]. (D) BrdU-positive cells 24 or 72 h after a single ECS compared with sham-handled controls [F(2, 9) = 24.575, P < 0.01]. Quantification of BrdU/RECA-positive cells following fluoxetine treatment (E) [F(1, 8) = 18.289, P < 0.01] or ECS (F) [F(2, 9) = 6.358, P < 0.05; n = 4–5 per group in each experiment]. ∗, P ≤ 0.05; ∗∗, P ≤ 0.01; +, P ≤ 0.1; n.s., P > 0.1.