Use este identificador para citar ou linkar para este item: http://www.repositorio.ufc.br/handle/riufc/19486
Título: Antimanic-like activity of candesartan in mice : possible involvement of antioxidant, anti-inflammatory and neurotrophic mechanisms
Autor(es): Gomes, Júlia Ariana de Souza
Souza, Greicy Coelho de
Berk, Michael
Cavalcante, Lígia Menezes
Sousa, Francisca Cléa F. de
Budni, Josiane
Lucena, David Freitas de
Quevedo, João
Carvalho, André F.
Macêdo, Danielle
Palavras-chave: Antioxidantes
Antioxidant
Antinflamatório
Data do documento: Nov-2015
Editor: European Neuropsychopharmacology
Citação: GOMES, J. A. S. ; SOUZA, G. C. ; BERK, M. ; CAVALCANTE, L. M. ; SOUSA, F. C. F. ; BUDNIE, J. ; LUCENA, D. F. ; QUEVEDO, J. ; CARVALHO, A. F. ; MACÊDO, D. (2015)
Abstract: Activation of the brain angiotensin II type 1 receptor (AT1R) triggers pro-oxidant and pro-inflammatory mechanisms which are involved in the neurobiology of bipolar disorder (BD). Candesartan (CDS) is an AT1 receptor antagonist with potential neuroprotective properties. Herein we investigated CDS effects against oxidative, neurotrophic inflammatory and cognitive effects of amphetamine (AMPH)-induced mania. In the reversal protocol adult mice were given AMPH 2 mg/kg i.p. or saline and between days 8 and 14 received CDS 0.1, 0.3 or 1 mg/kg orally, lithium (Li) 47.5 mg/kg i.p., or saline. In the prevention treatment, mice were pretreated with CDS, Li or saline prior to AMPH. Locomotor activity and working memory performance were assessed. Glutathione (GSH), thiobarbituric acid-reactive substance (TBARS) and TNF-α levels were evaluated in the hippocampus (HC) and cerebellar vermis (CV). Brain-derived neurotrophic factor (BDNF) and glycogen synthase kinase 3-beta (GSK-3beta) levels were measured in the HC. CDS and Li prevented and reversed the AMPH-induced increases in locomotor activity. Only CDS prevented and reversed AMPH-induced working memory deficits. CDS prevented AMPH-induced alterations in GSH (HC and CV), TBARS (HC and CV), TNF-α (HC and CV) and BDNF (HC) levels. Li prevented alterations in BDNF and phospho-Ser9-GSK3beta. CDS reversed AMPH-induced alterations in GSH (HC and CV), TBARS (HC), TNF-α (CV) and BDNF levels. Li reversed AMPH-induced alterations in TNF-α (HC and CV) and BDNF (HC) levels. CDS is effective in reversing and preventing AMPH-induced behavioral and biochemical alterations, providing a rationale for the design of clinical trials investigating CDS׳s possible therapeutic effects.
Descrição: GOMES, Júlia Ariana de Souza et al. Antimanic-like activity of candesartan in mice : possible involvement of antioxidant, anti-inflammatory and neurotrophic mechanisms. European Neuropsychopharmacology, v. 25, n. 11, p. 2086-2097, nov., 2015.
URI: 1873-7862
http://www.repositorio.ufc.br/handle/riufc/19486
ISSN: 0924-977X
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