Ketamine's potential mechanism of action for rapid antidepressive effects – a focus on neuroplasticity

Research surrounding ketamine has demonstrated its potential to induce rapid and significant antidepressant effects for patients with major depressive disorder and treatment-resistant depression. However, out of the many speculated pathways that ketamine influences, the mechanism of action underlying its rapid antidepressant effect remains unclear. Administration of ketamine is associated with restoration of markers involved in molecular neuroplasticity, such as glutamate, AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors, mTOR (mechanistic target of rapamycin), BDNF (brain-derived neurotrophic factor), TrkB (tropomyosin receptor kinase B), VGF, eEF2K (eukaryotic elongation factor 2 kinase), p70S6K (p70 ribosomal S6 kinase), GSK-3 (glycogen synthase kinase 3), Erk, and microRNAs. The changes are observed with rapid mood improvements in patients and behavioral changes in animal models of depression. This chapter summarizes recent literature regarding ketamine's potential mechanism of action to suggest a robust relationship between rapid antidepressant effects and ketamine-induced enhancement of molecular neuroplasticity.