Advantages of the Alpha-lipoic Acid Association with Chlorpromazine in a Model of Schizophrenia Induced by Ketamine in Rats: Behavioral and Oxidative Stress evidences

被引:16
作者
Leite Sampaio, Luis Rafael [1 ,2 ]
Mauricio Sales Cysne Filho, Francisco [3 ]
de Almeida, Jamily Cunha [3 ]
Diniz, Danilo dos Santos [1 ]
Vasconcelos Patrocinio, Claudio Felipe [4 ]
Soares de Sousa, Caren Nadia [1 ]
Azevedo Patrocinio, Manoel Claudio [4 ]
Macedo, Danielle [1 ]
Mendes Vasconcelos, Silvania Maria [1 ]
机构
[1] Univ Fed Ceara, Dept Physiol & Pharmacol, Drug Res & Dev Ctr, Neuropsychopharmacol Lab,Fac Med, Fortaleza, Ceara, Brazil
[2] Reg Univ Cariri, Ctr Biol & Hlth Sci, Cariri, CE, Brazil
[3] Univ Fortaleza, Fortaleza, Ceara, Brazil
[4] Univ Ctr Christus Unichristus, Sch Med, Fortaleza, Ceara, Brazil
关键词
schizophrenia; Hippocampus; oxidative stress; ketamine; chlorpromazine; alpha-lipoic acid; EXPERIMENTAL PSYCHOSIS MODEL; PREPULSE INHIBITION; NITRIC-OXIDE; ANTIOXIDATIVE DEFENSE; RECEPTOR ANTAGONISTS; ANIMAL-MODEL; IN-VITRO; BRAIN; MICE; MYELOPEROXIDASE;
D O I
10.1016/j.neuroscience.2018.01.008
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Schizophrenia is a chronic mental disorder reported to compromise about 1% of the world's population. Although its pathophysiological process is not completely elucidated, evidence showing the presence of an oxidative imbalance has been increasingly highlighted in the literature. Thus, the use of antioxidant substances may be of importance for schizophrenia treatment. The objective of this study was to evaluate the behavioral and oxidative alterations by the combination of chlorpromazine (CP) and alpha-lipoic acid (ALA), a potent antioxidant, in the ketamine (KET) model of schizophrenia in rats. Male Wistar rats (200-300 g) were treated for 10 days with saline, CP or ALA alone or in combination with CP previous to KET and the behavioral (open field, Y-maze and PPI tests) and oxidative tests were performed on the last day of treatment. The results showed that KET induced hyperlocomotion, impaired working memory and decreased PPI. CP alone or in combination with ALA prevented KET-induced behavioral effects. In addition, the administration of KET decreased GSH and increased nitrite, lipid peroxidation and myeloperoxidase activity. CP alone or combined with ALA prevented the oxidative alterations induced by KET. In conclusion, the treatment with KET in rats induced behavioral impairments accompanied by hippocampal oxidative alterations, possibly related to NMDA receptors hypofunction. Besides that, CP alone or combined with ALA prevented these effects, showing a beneficial activity as antipsychotic agents. (C) 2018 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:72 / 81
页数:10
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