Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/49607

TitleThe modulation of adult neuroplasticity is involved in the mood-improving actions of atypical antipsychotics in an animal model of depression
Author(s)Morais, Mónica Susana Dias
Patrício, Patrícia Carvalho
Pinheiro, António Maria Restolho Mateus
Alves, Nuno Dinis Lopes Oliveira
Santos, Ana Rita Machado dos
Correia, Joana Sofia Silva
Pereira, J.
Pinto, Luísa
Sousa, Nuno
Peixoto, João Miguel Seiça Bessa
Issue date2-Jun-2017
PublisherNature Publishing Group
JournalTranslational Psychiatry
CitationMorais, M., Patrício, P., Mateus-Pinheiro, A., Alves, N. D., Machado-Santos, A. R., Correia, J. S., ... & Bessa, J. M. (2017). The modulation of adult neuroplasticity is involved in the mood-improving actions of atypical antipsychotics in an animal model of depression. Translational Psychiatry, 7(6), e1146
Abstract(s)Depression is a prevalent psychiatric disorder with an increasing impact in global public health. However, a large proportion of patients treated with currently available antidepressant drugs fail to achieve remission. Recently, antipsychotic drugs have received approval for the treatment of antidepressant-resistant forms of major depression. The modulation of adult neuroplasticity, namely hippocampal neurogenesis and neuronal remodeling, has been considered to have a key role in the therapeutic effects of antidepressants. However, the impact of antipsychotic drugs on these neuroplastic mechanisms remains largely unexplored. In this study, an unpredictable chronic mild stress protocol was used to induce a depressive-like phenotype in rats. In the last 3 weeks of stress exposure, animals were treated with two different antipsychotics: haloperidol (a classical antipsychotic) and clozapine (an atypical antipsychotic). We demonstrated that clozapine improved both measures of depressive-like behavior (behavior despair and anhedonia), whereas haloperidol aggravated learned helplessness in the forced-swimming test and behavior flexibility in a cognitive task. Importantly, an upregulation of adult neurogenesis and neuronal survival was observed in animals treated with clozapine, whereas haloperidol promoted a downregulation of these processes. Furthermore, clozapine was able to re-establish the stress-induced impairments in neuronal structure and gene expression in the hippocampus and prefrontal cortex. These results demonstrate the modulation of adult neuroplasticity by antipsychotics in an animal model of depression, revealing that the atypical antipsychotic drug clozapine reverts the behavioral effects of chronic stress by improving adult neurogenesis, cell survival and neuronal reorganization.
TypeArticle
URIhttp://hdl.handle.net/1822/49607
DOI10.1038/tp.2017.120
ISSN1662-5153
Publisher versionhttps://www.nature.com/articles/tp2017120
Peer-Reviewedyes
AccessOpen access
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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