Document Detail


Maintenance treatment with fluoxetine is necessary to sustain normal levels of synaptic markers in an experimental model of depression: correlation with behavioral response.
MedLine Citation:
PMID:  17955054     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Dysfunction of hippocampal plasticity has been proposed to play a critical role in the pathophysiology of depression. However, antidepressant drug effects on synaptic plasticity and cytoskeletal remodeling remain controversial. The aim of the present study was to evaluate in animals exposed to the learned helplessness (LH) paradigm, an accepted experimental model of depression, the effect of chronic treatment with fluoxetine (FLX) on synaptic and cytoskeletal proteins known to undergo plastic changes. Synaptophysin (SYN), postsynaptic density 95 (PSD-95), axon growth-associated protein 43 (GAP-43), and cytoskeletal proteins (intermediate neurofilaments and MAP-2) were studied in the hippocampus by immunohistochemistry. Whereas LH animals treated 21 days with saline (LH-S group) displayed diminished SYN and PSD-95 immunostainings in the CA3 but not in the DG, chronic treatment with FLX not only reversed the despaired behavior induced by exposure to LH paradigm, but also fully recovered SYN and PSD-95 labeling to control values. Similar results were obtained for the axonal remodeling marker GAP-43. FLX treatment did not modify either the decreased light neurofilament subunit (NFL) observed in the hippocampus of LH animals or any other cytoskeletal protein studied. When FLX treatment was withdrawn for 90 days in those LH-FLX animals in which reversion of despair had been observed at day 25, recurrence of despaired behavior was found accompanied by decreased SYN, PSD-95, and NFL labelings. Results indicate that the synapse remodeling induced by FLX in the CA3 region could underlie its behavioral efficacy despite the absence of cytoskeletal remodeling and that the stability of synaptic changes would depend on the continuous administration of the drug.
Authors:
Analía Reinés; Marina Cereseto; Alejandro Ferrero; Laura Sifonios; Maria Fernanda Podestá; Silvia Wikinski
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-10-17
Journal Detail:
Title:  Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology     Volume:  33     ISSN:  0893-133X     ISO Abbreviation:  Neuropsychopharmacology     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-06-12     Completed Date:  2008-09-02     Revised Date:  2011-05-18    
Medline Journal Info:
Nlm Unique ID:  8904907     Medline TA:  Neuropsychopharmacology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1896-908     Citation Subset:  IM    
Affiliation:
Instituto de Investigaciones Farmacológicas (ININFA), CONICET, Universidad de Buenos Aires, Buenos Aires, Argentina. areines@ffyb.uba.ar
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MeSH Terms
Descriptor/Qualifier:
Animals
Antidepressive Agents, Second-Generation / administration & dosage,  therapeutic use*
Axons / physiology
Behavior, Animal / drug effects*
Biological Markers
Cytoskeleton / drug effects,  pathology
Data Interpretation, Statistical
Depressive Disorder / drug therapy*,  metabolism,  psychology*
Fluoxetine / administration & dosage,  therapeutic use*
Helplessness, Learned*
Hippocampus / drug effects,  metabolism,  physiopathology
Image Processing, Computer-Assisted
Immunohistochemistry
Male
Neuronal Plasticity / drug effects
Rats
Rats, Wistar
Recurrence
Synapses / drug effects,  metabolism*
Tissue Fixation
Chemical
Reg. No./Substance:
0/Antidepressive Agents, Second-Generation; 0/Biological Markers; 54910-89-3/Fluoxetine

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


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