Ketamine as a Novel Antidepressant: From Synapse to Behavior

Recent reports of a rapid antidepressant effect of the glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine, even in treatment-resistant populations, has spurred translational therapeutic and neuroscience research aimed at elucidating ketamine’s mechanism of action. This article provides a concise overview of research findings that pertain to the effects of low-dose ketamine at the cellular, neurocircuitry and behavioral levels and describes an integrated model of the action of ketamine in depression…

Low-dose ketamine appears to enhance the strength of cortical synapses through NMDAR and AMPAR-dependent and neurotrophic mechanisms and may rapidly reverse prefrontal cortical deficits in depression at the neurocircuit level, leading to an amelioration of clinical symptoms.

… Translational neuroscience approaches using ketamine as a model of rapid antidepressant action hold considerable potential to advance treatment discovery for MDD.

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