Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/64291

TitleThe mood-improving actions of antidepressants do not depend on neurogenesis but are associated with neuronal remodeling
Author(s)Bessa, J. M.
Ferreira, D.
Melo, I.
Marques, F.
Cerqueira, João José
Palha, Joana Almeida
Almeida, O. F. X.
Sousa, Nuno
KeywordsAffect
Analysis of Variance
Animals
Antidepressive Agents
Antidiuretic Hormone Receptor Antagonists
Behavior, Animal
Cytostatic Agents
Depression
Drug Combinations
Fluoxetine
Hippocampus
Imipramine
Indoles
Male
Methylazoxymethanol Acetate
Mitosis
Neurogenesis
Neuronal Plasticity
Prefrontal Cortex
Pyrrolidines
Rats
Rats, Wistar
Receptors, Corticotropin-Releasing Hormone
Stress, Psychological
neuroplasticity
antidepressant
NCAM
synapsin 1
Issue dateAug-2009
PublisherNature Publishing Group
JournalMolecular Psychiatry
Abstract(s)The mechanisms underlying the initiation/onset of, and the recovery from, depression are still largely unknown; views that neurogenesis in the hippocampus may be important for the pathogenesis and amelioration of depressive symptoms have gained currency over the years although the original evidence has been challenged. In this study, an unpredictable chronic mild stress protocol was used to induce a depressive-like phenotype in rats. In the last 2 weeks of stress exposure, animals were treated with the antidepressants fluoxetine, imipramine, CP 156,526 or SSR 1494515, alone or combined with methylazoxymethanol, a cytostatic agent used to arrest neurogenesis. We found that antidepressants retain their therapeutic efficacy in reducing both measured indices of depression-like behavior (learned helplessness and anhedonia), even when neurogenesis is blocked. Instead, our experiments suggest re-establishment of neuronal plasticity (dendritic remodeling and synaptic contacts) in the hippocampus and prefrontal cortex, rather than neurogenesis, as the basis for the restoration of behavioral homeostasis by antidepressants.
TypeArticle
URIhttp://hdl.handle.net/1822/64291
e-ISBN1476-5578
DOI10.1038/mp.2008.119
ISSN1359-4184
Peer-Reviewedyes
AccessOpen access
Appears in Collections:ICVS - Artigos em revistas internacionais / Papers in international journals

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