PMID- 20724638
OWN - NLM
STAT- MEDLINE
DCOM- 20100902
LR  - 20220408
IS  - 1095-9203 (Electronic)
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 329
IP  - 5994
DP  - 2010 Aug 20
TI  - mTOR-dependent synapse formation underlies the rapid antidepressant effects of 
      NMDA antagonists.
PG  - 959-64
LID - 10.1126/science.1190287 [doi]
AB  - 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.
FAU - Li, Nanxin
AU  - Li N
AD  - Laboratory of Molecular Psychiatry, Center for Genes and Behavior, Department of 
      Psychiatry, Yale University School of Medicine, 34 Park Street, New Haven, CT 
      06508, USA.
FAU - Lee, Boyoung
AU  - Lee B
FAU - Liu, Rong-Jian
AU  - Liu RJ
FAU - Banasr, Mounira
AU  - Banasr M
FAU - Dwyer, Jason M
AU  - Dwyer JM
FAU - Iwata, Masaaki
AU  - Iwata M
FAU - Li, Xiao-Yuan
AU  - Li XY
FAU - Aghajanian, George
AU  - Aghajanian G
FAU - Duman, Ronald S
AU  - Duman RS
LA  - eng
GR  - P01 MH025642/MH/NIMH NIH HHS/United States
GR  - 2P01 MH25642/MH/NIMH NIH HHS/United States
GR  - P01 MH025642-30/MH/NIMH NIH HHS/United States
GR  - R01 MH045481-13/MH/NIMH NIH HHS/United States
GR  - MH45481/MH/NIMH NIH HHS/United States
GR  - R01 MH045481-14/MH/NIMH NIH HHS/United States
GR  - P01 MH025642-32/MH/NIMH NIH HHS/United States
GR  - R01 MH045481-15/MH/NIMH NIH HHS/United States
GR  - R01 MH045481/MH/NIMH NIH HHS/United States
GR  - P01 MH025642-31/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (Antidepressive Agents)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Neuropeptides)
RN  - 0 (Phenols)
RN  - 0 (Piperidines)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Ro 25-6981)
RN  - 690G0D6V8H (Ketamine)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
CIN - Science. 2010 Aug 20;329(5994):913-4. PMID: 20724626
CIN - Nat Rev Neurosci. 2010 Oct;11(10):666. PMID: 21080533
CIN - Expert Rev Neurother. 2011 Jan;11(1):33-6. PMID: 21158553
MH  - Animals
MH  - Antidepressive Agents/pharmacokinetics/*pharmacology
MH  - Dendritic Spines/drug effects/metabolism
MH  - Depression/drug therapy/metabolism
MH  - Intracellular Signaling Peptides and Proteins/agonists
MH  - Ketamine/pharmacokinetics/*pharmacology
MH  - Male
MH  - Neurons/drug effects/metabolism
MH  - Neuropeptides/*biosynthesis/metabolism
MH  - Phenols/pharmacology
MH  - Piperidines/pharmacology
MH  - Protein Biosynthesis/drug effects
MH  - Protein Serine-Threonine Kinases
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors
MH  - Signal Transduction/drug effects
MH  - Sirolimus/pharmacology
MH  - Synapses/*drug effects/metabolism
MH  - TOR Serine-Threonine Kinases
MH  - Time Factors
PMC - PMC3116441
MID - NIHMS293810
EDAT- 2010/08/21 06:00
MHDA- 2010/09/03 06:00
PMCR- 2011/06/16
CRDT- 2010/08/21 06:00
PHST- 2010/08/21 06:00 [entrez]
PHST- 2010/08/21 06:00 [pubmed]
PHST- 2010/09/03 06:00 [medline]
PHST- 2011/06/16 00:00 [pmc-release]
AID - 329/5994/959 [pii]
AID - 10.1126/science.1190287 [doi]
PST - ppublish
SO  - Science. 2010 Aug 20;329(5994):959-64. doi: 10.1126/science.1190287.