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. 2021 Apr 30;15:657714. doi: 10.3389/fnins.2021.657714

FIGURE 2.

FIGURE 2

Schematic representation of some potential mechanisms involved in the antidepressant actions of ketamine. (1): Ketamine reduces NMDA receptor mediated stimulation of GABA interneurons reducing the inhibitory action on presynaptic glutamatergic neuron; (2) the reduced inhibition produces a rapid glutamate burst acting on AMPA receptors located on pyramidal neurons; (3) Such activation leads to the opening of voltage-dependent calcium channels (VDCC) that stimulate BDNF; (4) BDNF induce the translation and synthesis of key synaptic proteins in synaptogenesis and maturation of dendritic spines, including GluA1 and PSD95), via the TrkB/Flk-1 - mTORC1-signaling pathway; (5) ketamine acting as NMDA inhibited the eukaryotic elongation factor2 (eEF2) kinase, resulting in reduced eEF2 phosphorylation and increased BDNF translation and protein synthesis; (6) ketamine metabolite can stimulate AMPA receptors independently of NMDA receptor blockade by ketamine; (7) kainate receptor can contribute to Na+ and Ca++ entry, neuronal depolarization and postsynaptic responses.