Neuropsychopharmacology Laboratory, Department of Physiology and Pharmacology, Drug Research and Development Center, Faculty of Medicine, Federal University of Ceará Fortaleza, CE, Brazil; Center of Biological and Health Sciences, Regional University of Cariri Cariri, CE, Brazil.
University of Fortaleza Fortaleza, CE, Brazil.
Neuroscience. 2018 Mar 1;373:72-81. doi: 10.1016/j.neuroscience.2018.01.008. Epub 2018 Jan 11.
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.
精神分裂症是一种慢性精神障碍，据报道，其影响了全球约 1%的人口。尽管其病理生理过程尚未完全阐明，但越来越多的证据表明存在氧化失衡。因此，使用抗氧化物质可能对精神分裂症的治疗具有重要意义。本研究旨在评估氯丙嗪（CP）和α-硫辛酸（ALA）联合使用对精神分裂症大鼠模型中氯丙嗪和酮（KET）的行为和氧化改变的影响。雄性 Wistar 大鼠（200-300g）用生理盐水、CP 或 ALA 单独或与 CP 联合治疗 10 天，然后进行 KET 治疗，并在最后一天进行行为（旷场、Y 迷宫和 PPI 测试）和氧化测试。结果表明，KET 诱导了过度活跃、工作记忆受损和 PPI 降低。CP 单独或与 ALA 联合使用可预防 KET 诱导的行为效应。此外，KET 的给药降低了 GSH，增加了亚硝酸盐、脂质过氧化和髓过氧化物酶活性。CP 单独或联合 ALA 可预防 KET 引起的氧化改变。综上所述，KET 处理大鼠诱导了行为障碍，同时伴有海马氧化改变，可能与 NMDA 受体功能低下有关。此外，CP 单独或联合 ALA 可预防这些作用，表现出作为抗精神病药物的有益活性。
