How does ketamine elicit a rapid antidepressant response?

A single sub-psychotomimetic dose of ketamine, an ionotropic glutamatergic n-methyl-d-aspartate (NMDA) receptor antagonist, produces a fast-acting antidepressant response in patients suffering from major depressive disorder. Depressed patients report alleviation of core symptoms within two hours of a single low-dose intravenous infusion of ketamine with effects lasting up to two weeks. The rapidity of ketamine action implies that major symptoms of depression can be alleviated without substantial structural plasticity or circuit rewiring. Therefore, the ability of ketamine to exert a rapid effect provides a unique opportunity to elucidate the types of acute synaptic plasticity changes that can be recruited to counter depression symptoms.