Document Detail

Signaling pathways underlying the rapid antidepressant actions of ketamine.
MedLine Citation:
PMID:  21907221     Owner:  NLM     Status:  MEDLINE    
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'.
Ronald S Duman; Nanxin Li; Rong-Jian Liu; Vanja Duric; George Aghajanian
Publication Detail:
Type:  Journal Article; Review     Date:  2011-09-02
Journal Detail:
Title:  Neuropharmacology     Volume:  62     ISSN:  1873-7064     ISO Abbreviation:  Neuropharmacology     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2011-10-17     Completed Date:  2012-08-13     Revised Date:  2014-01-07    
Medline Journal Info:
Nlm Unique ID:  0236217     Medline TA:  Neuropharmacology     Country:  England    
Other Details:
Languages:  eng     Pagination:  35-41     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
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MeSH Terms
Antidepressive Agents / pharmacology*,  therapeutic use
Depression / drug therapy,  pathology
Gene Expression Regulation / drug effects
Ketamine / pharmacology*,  therapeutic use
Models, Biological
Neurogenesis / drug effects*
Neurons / drug effects
Signal Transduction / drug effects*
Synapses / drug effects
Grant Support
R01 MH093897/MH/NIMH NIH HHS; R01 MH093897-01/MH/NIMH NIH HHS; R01 MH093897-02/MH/NIMH NIH HHS
Reg. No./Substance:
0/Antidepressive Agents; 690G0D6V8H/Ketamine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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