title: Hippocampal VEGF is necessary for antidepressant-like behaviors but not sufficient for antidepressant-like effects of ketamine in rats.
abstract: We investigated the effects of ketamine on both the temporal and spatial profiles of neural precursor cells located in the hippocampus, and on antidepressant-like behaviors in rats. A single dose of ketamine resulted in a significant increase in the number of 5-bromo-2-deoxyuridine-positive (BrdU(+)) cells in the dentate gyrus (DG) of rats at 24h, but not at 28days, after treatment completion. Ketamine caused antidepressant-like behaviors in the forced swim test (FST) and novelty suppressed feeding test (NSFT). Viral-mediated hippocampal knockdown of vascular endothelial growth factor (VEGF) produced depressive-like behaviors in the FST and NSFT, which were partially recovered by ketamine to the level observed in the control group. The behavioral effects of VEGF knock down were accompanied by a decrease in hippocampal neurogenesis, which was also partially recovered by ketamine. Our results suggest that basal hippocampal VEGF expression is necessary for ketamine-induced antidepressant-like behaviors in rats, but ketamine-induced VEGF expression only partially contributes to hippocampal neurogenesis and the antidepressant-like effects of ketamine.
authors.affiliation: Department of Biochemistry and Molecular Biology, Hanyang University, 17 Haengdang-dong, Sungdong-gu, Seoul 133-791, Republic of Korea.
authors.forename: Miyeon
authors.initials: M
authors.lastname: Choi
authors.affiliation: Graduate School of Biomedical Science and Engineering, Hanyang University, 17 Haengdang-dong, Sungdong-gu, Seoul 133-791, Republic of Korea.
authors.forename: Seung Hoon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, College of Medicine, Hanyang University, 17 Haengdang-dong, Sungdong-gu, Seoul 133-791, Republic of Korea.
authors.forename: Ho Lee
authors.initials: HL
authors.lastname: Chang
authors.affiliation: Department of Biochemistry and Molecular Biology, Hanyang University, 17 Haengdang-dong, Sungdong-gu, Seoul 133-791, Republic of Korea; Graduate School of Biomedical Science and Engineering, Hanyang University, 17 Haengdang-dong, Sungdong-gu, Seoul 133-791, Republic of Korea. Electronic address: hyeonson@hanyang.ac.kr.
authors.forename: Hyeon
authors.initials: H
authors.lastname: Son
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D018891:Dentate Gyrus / Q000187:drug effects / Q000503:physiopathology; D003863:Depression / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D055785:Gene Knockdown Techniques; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D055495:Neurogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D000928:Antidepressive Agents; D018691:Excitatory Amino Acid Antagonists; D042461:Vascular Endothelial Growth Factor A; D007649:Ketamine
keywords: Depression; Ketamine; Neurogenesis; Rat; VEGF