Ketamine has been found to have rapid and potent antidepressant activity. However, despite the ubiquitous brain expression of its molecular target, the N-methyl-d-aspartate receptor (NMDAR), it was not clear whether there is a selective, primary site for ketamine's antidepressant action. We found that ketamine injection in depressive-like mice specifically blocks NMDARs in lateral habenular...
Substantial clinical evidence has unravelled the superior antidepressant efficacy of ketamine: in comparison to traditional antidepressants targeting the monoamine systems, ketamine, as an N-methyl-d-aspartate receptor (NMDAR) antagonist, acts much faster and more potently. Surrounding the antidepressant mechanisms of ketamine, there is ample evidence supporting an NMDAR-antagonism-based...
The discrepancy between the short half-life of ketamine and its long-lasting effects is due to ketamine being trapped in NMDA receptors, and its release depends on neural activity in the lateral habenula. Ketamine, an N -methyl- d -aspartate receptor (NMDAR) antagonist^ 1 , has revolutionized the treatment of depression because of its potent, rapid and sustained antidepressant effects^ 2 – 4 ....
The rapid antidepressant effect of ketamine is arguably one of the most significant advances in the mental health field in the last half century. However, its mechanism of action has remained elusive. Here, we describe our latest discovery on how ketamine blocks N-methyl-D-aspartate receptor (NMDAR)-dependent burst firing of an "antireward" center in the brain, the lateral habenula (LHb), to...