Figure 2.

The proposed mechanism of ketamine’s antidepressant effect, according to [54], involves the suppression of tonic GABAergic activity (1), which leads to a surge in glutamate release and metabolism (2); this increased glutamate activity, through AMPA receptors (whose surface expression may be boosted by the reduced spontaneous activity of NMDA receptors) (3), promotes BDNF-dependent (4) synaptic growth (5), ultimately contributing to rapid and sustained antidepressant effects. Akt, protein kinase B; ERK, extracellular signal-regulated kinase; mTOR, mammalian/mechanistic target of rapamycin; TrkB, tropomyosin kinase B.