Antimanic-like activity of candesartan in mice: possible involvement of antioxidant, anti-inflammatory and neurotrophic mechanisms

de Souza Gomes, Julia Ariana, de Souza, Greicy Coehlo, Berk, Michael, Cavalcante, Ligia Menezes, de Sousa, Francisca Clea, Budni, Josiane, de Lucena, David Freitas, Quevedo, Joao, Carvalho, Andre F. and Macêdo, Danielle 2015, Antimanic-like activity of candesartan in mice: possible involvement of antioxidant, anti-inflammatory and neurotrophic mechanisms, European neuropsychopharmacology, vol. 25, no. 11, pp. 2086-2097, doi: 10.1016/j.euroneuro.2015.08.005.

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Title Antimanic-like activity of candesartan in mice: possible involvement of antioxidant, anti-inflammatory and neurotrophic mechanisms
Author(s) de Souza Gomes, Julia Ariana
de Souza, Greicy Coehlo
Berk, MichaelORCID iD for Berk, Michael
Cavalcante, Ligia Menezes
de Sousa, Francisca Clea
Budni, Josiane
de Lucena, David Freitas
Quevedo, Joao
Carvalho, Andre F.
Macêdo, Danielle
Journal name European neuropsychopharmacology
Volume number 25
Issue number 11
Start page 2086
End page 2097
Total pages 12
Publisher Elsevier
Place of publication Amsterdam, The Netherlands
Publication date 2015-11
ISSN 1873-7862
Keyword(s) Anti-inflammatory
Summary 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 2mg/kg i.p. or saline and between days 8 and 14 received CDS 0.1, 0.3 or 1mg/kg orally, lithium (Li) 47.5mg/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.
Language eng
DOI 10.1016/j.euroneuro.2015.08.005
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 929999 Health not elsewhere classified
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2015, Elsevier
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Document type: Journal Article
Collections: Faculty of Health
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