Abstract
Currently available antidepressants based on the monoamine hypothesis of depression (e. g. selective serotonin reuptake inhibitors) have significant limitations, including delayed onset of therapeutic response and low efficacy : approximately one‐third of depressed patients fail to respond to multiple antidepressant treatments and are considered treatment‐resistant. In contrast, ketamine, an N‐methyl‐D‐aspartate receptor antagonist, produces rapid and sustained antidepressant effects in patients with treatment‐resistant depression. Previous preclinical studies have demonstrated that brain‐derived neurotrophic factor (BDNF) ‐mediated neuronal plasticity in the medial prefrontal cortex (mPFC) is essential for the antidepressant actions of ketamine. We have recently shown that neuronal vascular endothelial growth factor (VEGF) in the mPFC also plays an important role in the antidepressant and neuroplastic effects of ketamine in rodents. Moreover, we have demonstrated that a heterologous interplay between BDNF and VEGF signaling in the mPFC is required to produce ketamine‐like antidepressant effects of these neurotrophic factors. This review provides an overview of the roles of BDNF and VEGF in the antidepressant actions of ketamine, especially focusing on our recent findings.
