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. Attached Files Name Description MIMEType Size Downloads 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, Michael orcid.org/0000-0002-5554-6946 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 Antioxidant BDNF Candesartan GSK3beta Mania 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 Persistent URL http://hdl.handle.net/10536/DRO/DU:30078425 Document type: Journal Article Collections: Faculty of Health School of Medicine Related Links Link Description Connect to published version Go to link with your DU access privileges   Connect to Elements publication management system Go to link with your DU access privileges     Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved. Versions Version Filter Type Thu, 24 Sep 2015, 12:44:59 EST Fri, 25 Sep 2015, 05:00:38 EST Fri, 25 Sep 2015, 06:12:29 EST Fri, 09 Oct 2015, 13:07:25 EST Fri, 09 Oct 2015, 13:08:47 EST Fri, 09 Oct 2015, 13:30:02 EST Mon, 18 Jul 2016, 15:44:47 EST Tue, 26 Jul 2016, 12:12:07 EST Tue, 26 Jul 2016, 12:14:03 EST Fri, 29 Jul 2016, 12:32:42 EST Wed, 12 Oct 2016, 14:06:19 EST Wed, 01 Mar 2017, 07:21:37 EST Fri, 21 Apr 2017, 07:14:07 EST Filtered Full Citation counts:   Cited 23 times in TR Web of Science Cited 22 times in Scopus Search Google Scholar Access Statistics: 593 Abstract Views, 4 File Downloads  -  Detailed Statistics Created: Thu, 24 Sep 2015, 12:44:59 EST