PMID- 21907221
OWN - NLM
STAT- MEDLINE
DCOM- 20120813
LR  - 20240417
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Print)
IS  - 0028-3908 (Linking)
VI  - 62
IP  - 1
DP  - 2012 Jan
TI  - Signaling pathways underlying the rapid antidepressant actions of ketamine.
PG  - 35-41
LID - 10.1016/j.neuropharm.2011.08.044 [doi]
AB  - Currently available medications have significant limitations, most notably low 
      response rate and time lag for treatment response. Recent clinical studies have 
      demonstrated that ketamine, an NMDA receptor antagonist produces a rapid 
      antidepressant response (within hours) and is effective in treatment resistant 
      depressed patients. Molecular and cellular studies in rodent models demonstrate 
      that ketamine rapidly increases synaptogenesis, including increased density and 
      function of spine synapses, in the prefrontal cortex (PFC). Ketamine also 
      produces rapid antidepressant actions in behavioral models of depression, and 
      reverses the deficits in synapse number and behavior resulting from chronic 
      stress exposure. These effects of ketamine are accompanied by stimulation of the 
      mammalian target of rapamycin (mTOR), and increased levels of synaptic proteins. 
      Together these studies indicate that ketamine rapidly reverses the atrophy of 
      spines in the PFC and thereby causes a functional reconnection of neurons that 
      underlies the rapid behavioral responses. These findings identify new targets for 
      rapid acting antidepressants that are safer than ketamine. This article is part 
      of a Special Issue entitled 'Anxiety and Depression'.
CI  - Copyright (c) 2011 Elsevier Ltd. All rights reserved.
FAU - Duman, Ronald S
AU  - Duman RS
AD  - Departments of Psychiatry and Neurobiology, Yale University School of Medicine, 
      34 Park Street, New Haven, CT 06508, USA. ronald.duman@yale.edu
FAU - Li, Nanxin
AU  - Li N
FAU - Liu, Rong-Jian
AU  - Liu RJ
FAU - Duric, Vanja
AU  - Duric V
FAU - Aghajanian, George
AU  - Aghajanian G
LA  - eng
GR  - R01 MH093897/MH/NIMH NIH HHS/United States
GR  - R01 MH093897-01/MH/NIMH NIH HHS/United States
GR  - R01 MH093897-02/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20110902
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Antidepressive Agents)
RN  - 690G0D6V8H (Ketamine)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/*pharmacology/therapeutic use
MH  - Depression/drug therapy/pathology
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Ketamine/*pharmacology/therapeutic use
MH  - Models, Biological
MH  - Neurogenesis/*drug effects
MH  - Neurons/drug effects
MH  - Signal Transduction/*drug effects
MH  - Synapses/drug effects
PMC - PMC3195863
MID - NIHMS327857
EDAT- 2011/09/13 06:00
MHDA- 2012/08/14 06:00
PMCR- 2013/01/01
CRDT- 2011/09/13 06:00
PHST- 2011/07/07 00:00 [received]
PHST- 2011/08/23 00:00 [revised]
PHST- 2011/08/23 00:00 [accepted]
PHST- 2011/09/13 06:00 [entrez]
PHST- 2011/09/13 06:00 [pubmed]
PHST- 2012/08/14 06:00 [medline]
PHST- 2013/01/01 00:00 [pmc-release]
AID - S0028-3908(11)00377-7 [pii]
AID - 10.1016/j.neuropharm.2011.08.044 [doi]
PST - ppublish
SO  - Neuropharmacology. 2012 Jan;62(1):35-41. doi: 10.1016/j.neuropharm.2011.08.044. 
      Epub 2011 Sep 2.