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mTOR-dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists

Nanxin Li, Boyoung Lee, Rong-Jian Liu, Mounira Banasr, Jason M Dwyer, Masaaki Iwata, Xiao-Yuan Li, George Aghajanian, Ronald S Duman

Science. 2010 Aug 20;329(5994):959-64.

PMID: 20724638

Abstract:

The rapid antidepressant response after ketamine administration in treatment-resistant depressed patients suggests a possible new approach for treating mood disorders compared to the weeks or months required for standard medications. However, the mechanisms underlying this action of ketamine [a glutamate N-methyl-D-aspartic acid (NMDA) receptor antagonist] have not been identified. We observed that ketamine rapidly activated 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 rats. Moreover, blockade of mTOR signaling completely blocked ketamine induction of synaptogenesis and behavioral responses in models of depression. Our results demonstrate that these effects of ketamine are opposite to the synaptic deficits that result from exposure to stress and could contribute to the fast antidepressant actions of ketamine.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP6384925-A N-Methyl-D-aspartic acid N-Methyl-D-aspartic acid 6384-92-5 Price
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