报告题目：Rapid Antidepressant Effects of Ketamine Require Synaptic Protein Synthesis and Spine Formation
Division of Molecular Psychiatry，Department of Psychology，Yale University
The rapid antidepressant response seen following ketamine administration in treatment resistant depressed patients demonstrates a powerful new approach for treating mood disorders. However, the mechanisms underlying this surprising action of ketamine have not been identified. Here we report that ketamine rapidly activates the mammalian target of rapamycin (mTOR) pathway, leading to increased synaptic signaling proteins and increased number and function of new spine synapses in the prefrontal cortex of rat. Moreover, blockade of mTOR signaling completely blocks the actions of ketamine in behavioral models of depression. Our results demonstrate that these effects of ketamine are opposite to the synaptic deficits that result from exposure to stress and depression and could contribute to the fast antidepressant effects of ketamine.