Most treatments for depression require weeks or months to produce a therapeutic response, but a low dose of ketamine can do so within hours. Now scientists at the Yale University School of Medicine in New Haven, Conn, have uncovered the mechanism behind ketamine's fast-acting nature (Li N et al. Science. 2010;329:959-956).
Experiments in rats revealed that ketamine rapidly activates the brain's rapamycin, or mTOR, signaling pathway, which controls protein synthesis required for new synaptic connections between neurons. Specifically, ketamine's actions on this pathway restored connections between the rats’ prefrontal cortex neurons that had been damaged by chronic stress. The investigators could reverse these effects by simply blocking the mTOR signaling pathway.
Hampton T. Ketamine’s Success. JAMA. 2010;304(13):1432. doi:10.1001/jama.2010.1368