Uncovering the Underlying Mechanisms of Ketamine as a Novel Antidepressant
Frontiers in Pharmacology July 7, 2022 Songbai Xu, Xiaoxiao Yao, Bingjin Li et al. 50 citations
Ketamine, a drug that blocks N-methyl-D-aspartate receptors, produces rapid and lasting antidepressant effects in people with major depressive disorder and in animal models, but its use is limited by side effects like dissociation and psychosis-like experiences. The drug may work by enhancing signaling through another receptor type, AMPA receptors, in brain cells, possibly by reducing inhibition or blocking spontaneous NMDAR activity. It also activates pathways linked to brain plasticity and synapse formation, such as BDNF/TrkB and mTOR signaling. These processes may help restore the balance of excitatory and inhibitory signals in brain circuits disrupted in depression. Understanding these mechanisms could guide development of safer, more effective treatments.