Document Detail

Vascular endothelial growth factor signaling is required for the behavioral actions of antidepressant treatment: pharmacological and cellular characterization.
MedLine Citation:
PMID:  19553916     Owner:  NLM     Status:  MEDLINE    
This study extends earlier work on the role of vascular endothelial growth factor (VEGF) in the actions of antidepressant treatment in two key areas. First, by determining the requirement for VEGF in the actions of a 5-HT selective reuptake inhibitor (SSRI), fluoxetine in behavioral models of depression/antidepressant response; and second, by examining the role of the 5-HT1A receptor subtype in the regulation of VEGF, and the cellular localization of antidepressant regulation of VEGF expression. The results show that pharmacological inhibition of VEGF receptor signaling blocks the behavioral actions of fluoxetine in rats subjected to chronic unpredictable stress. Infusions of SU5416 or SU1498, two structurally dissimilar inhibitors of VEGF-Flk-1 receptor signaling, block the antidepressant effects of fluoxetine on sucrose preference, immobility in the forced swim test, and latency to feed in the novelty suppressed feeding paradigm. We also show that activation of 5-HT1A receptors is sufficient to induce VEGF expression and that a 5-HT1A antagonist blocks both the increase in VEGF and behavioral effects induced by fluoxetine. Finally, double labeling studies show that chronic fluoxetine administration increases VEGF expression in both neurons and endothelial cells in the hippocampus. Taken together these studies show that VEGF is necessary for the behavioral effects of the SSRI fluoxetine, as well as norepinephrine selective reuptake inhibitor, and that these effects may be mediated by 5-HT1A receptors located on neurons and endothelial cells.
Joshua Greene; Mounira Banasr; Boyoung Lee; Jennifer Warner-Schmidt; Ronald S Duman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2009-06-24
Journal Detail:
Title:  Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology     Volume:  34     ISSN:  1740-634X     ISO Abbreviation:  Neuropsychopharmacology     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-09-14     Completed Date:  2009-12-07     Revised Date:  2014-01-07    
Medline Journal Info:
Nlm Unique ID:  8904907     Medline TA:  Neuropsychopharmacology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2459-68     Citation Subset:  IM    
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MeSH Terms
Antidepressive Agents / pharmacology*
Depression / drug therapy*,  metabolism*
Endothelial Cells / drug effects,  metabolism
Fluoxetine / pharmacology*
Hippocampus / blood supply,  drug effects,  metabolism
Neurons / drug effects,  metabolism
Neuropsychological Tests
Random Allocation
Rats, Sprague-Dawley
Receptor, Serotonin, 5-HT1A / metabolism
Serotonin 5-HT1 Receptor Antagonists
Serotonin Uptake Inhibitors / pharmacology
Signal Transduction / drug effects
Stress, Psychological / drug therapy,  metabolism
Vascular Endothelial Growth Factor A / metabolism*
Vascular Endothelial Growth Factor Receptor-2 / metabolism
Grant Support
Reg. No./Substance:
0/Antidepressive Agents; 0/Serotonin 5-HT1 Receptor Antagonists; 0/Serotonin Uptake Inhibitors; 0/Vascular Endothelial Growth Factor A; 01K63SUP8D/Fluoxetine; 112692-38-3/Receptor, Serotonin, 5-HT1A; EC Endothelial Growth Factor Receptor-2

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

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