Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Science. 2010 Aug 20;329(5994):959-64. doi: 10.1126/science.1190287.

mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists.

Author information

  • 1Laboratory of Molecular Psychiatry, Center for Genes and Behavior, Department of Psychiatry, Yale University School of Medicine, 34 Park Street, New Haven, CT 06508, USA.

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.

Comment in

PMID:
20724638
[PubMed - indexed for MEDLINE]
PMCID:
PMC3116441
Free PMC Article

Images from this publication.See all images (4)Free text

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Publication Types, MeSH Terms, Substances, Grant Support

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk