Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
Oxid Med Cell Longev. 2010 Nov-Dec;3(6):421-7. doi: 10.4161/oxim.3.6.13446. Epub 2010 Nov 1.
Schizophrenia is a debilitating mental disorder characterized by positive (delusions, hallucinations, disorganized speech) and negative (affective flattering, avolition, and social withdrawal) symptoms as well as cognitive deficits. The frequency, severity, and topography characterize the disorder as heterogeneous, the pathophysiology of schizophrenia is poorly understood. Sub-anesthetic doses of ketamine produce hyperactivity, stereotypy, and abnormal social interaction and it is used as a model of schizophrenia. In this study, we induced an animal model by acute sub-anesthetic doses of ketamine and tested different behavioral parameters. We also evaluated the activity of creatine kinase (CK) in brain of rats treated with ketamine. Our results demonstrated that administration of 10, 25 and 50 mg/kg of ketamine induced an increase of covered distance in habituated and non-habituated rats to the behavioral apparatus. Ketamine administration induced significant social deficits and stereotypic behavioral in all doses tested. Finally we evaluated the effect of different doses of ketamine on creatinine kinase (CK) activity and we observed that CK activity is increased inspecific regions of the brain. Our study suggests that our animal model may be used as a model of schizophrenia and that cerebral energy metabolism might be altered in the brain of schizophrenic patients, probably leading to alterations that might be involved in the pathogenesis of schizophrenia.
精神分裂症是一种使人衰弱的精神障碍，其特征为阳性（妄想、幻觉、言语紊乱）和阴性（情感平淡、意志缺失和社会退缩）症状以及认知缺陷。该疾病的频率、严重程度和发病部位表现出异质性，其病理生理学尚未被充分理解。亚麻醉剂量的氯胺酮会引起过度活跃、刻板行为和异常的社会互动，因此被用作精神分裂症的模型。在这项研究中，我们通过急性给予亚麻醉剂量的氯胺酮诱导动物模型，并测试了不同的行为参数。我们还评估了氯胺酮处理的大鼠大脑中的肌酸激酶（CK）活性。我们的结果表明，给予 10、25 和 50mg/kg 的氯胺酮会增加习惯化和非习惯化大鼠对行为装置的覆盖距离。氯胺酮给药在所有测试剂量下均诱导出明显的社交缺陷和刻板行为。最后，我们评估了不同剂量的氯胺酮对肌酸激酶（CK）活性的影响，观察到特定脑区的 CK 活性增加。我们的研究表明，我们的动物模型可用于模拟精神分裂症，并且精神分裂症患者大脑中的脑能量代谢可能会发生改变，这可能导致与精神分裂症发病机制相关的变化。
