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The mood-improving actions of antidepressants do not depend on neurogenesis but are associated with neuronal remodeling

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Resumo: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.
Autores principais:Bessa, J. M.
Outros Autores:Ferreira, D.; Melo, I.; Marques, F.; Cerqueira, João José; Palha, Joana Almeida; Almeida, O. F. X.; Sousa, Nuno
Assunto:Affect 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
Ano:2009
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso aberto
Instituição associada:Universidade do Minho
Idioma:inglês
Origem:RepositóriUM - Universidade do Minho

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