Recently ketamine has come under focus for its notable effects treating depression. A new study seeks to identify the pathway that allows its rapid anti-depressant effects. The horse tranquilizer turned party drug may have found another niche. The study was published in Nature, funded by the National Key R&D program of China.
As this research is in its introductory stages, researchers used a mouse model instead of human subjects. To simulate depression symptoms, rats were specifically bred as “Congenitally Learned Helpless” and mice as “Chronic Restraint Stress”. The animals were then injected with Ketamine and their behavior or electrophysiology was examined.
The findings revealed that the ketamine works by inhibiting the NMDAR pathway, nicknamed the “anti-reward center”. Burst evoking stimulation of this pathway has been show to lead to depressive behavior and anhedonia. By inhibiting the NMDAR, downstream reward centers have been shown to quickly elevate mood and produce rapid acting anti-depressant effects.
This research does not address the question of what the long-term effects of ketamine are, and its utility may lie in helping to understand the pathways that regulate depressive mood rather than paving the way for ketamine prescriptions as an antidepressant, being that it has a significant potential for abuse (not to mention a sorted reputation).
Anti-depressants tend to focus on boosting serotonin and dopamine expression to elevate mood, but by understanding and manipulating the pathway that inhibits their expression, a more targeted and effective treatment can be administered. The discovery of the NMDAR antagonist and its rapid anti-depressant effects has been called the most important advance in psychiatry in the last century. We live in an age where clinical depression has become relatively commonplace, and the recently discovered effects of Ketamine as this critical antagonist cannot be ignored.
Yang Y, Cui Y, Sang K, Dong Y, Ni Z et. al. (2018) Ketamine blocks bursting in the lateral habenula to rapidly relieve depression. Nature 554: 317-22