Neurotrophic mechanisms underlying the rapid and sustained antidepressant actions of ketamine.
Pharmacology, Biochemistry and Behavior December 9, 2019 Satoshi Deyama, R. Duman 181 citations
Depression is linked to reduced levels of neurotrophic factors like BDNF and VEGF, which contribute to neuronal atrophy in brain regions such as the prefrontal cortex and hippocampus, and to decreased adult neurogenesis. Conventional antidepressants partially reverse these deficits by inducing BDNF or VEGF but have limitations, including a delayed therapeutic response and low efficacy. Ketamine, an NMDA receptor antagonist, produces rapid (within hours) and sustained (up to a week) antidepressant effects in treatment-resistant depression and rodent models. In rodents, ketamine quickly increases BDNF and VEGF release in the medial prefrontal cortex and hippocampus, boosting spine synapses and hippocampal neurogenesis. These neurotrophic actions appear to underlie ketamine's rapid and sustained antidepressant effects, pointing toward development of faster-acting antidepressants with fewer side effects.