Riegel Rafael E, Valvassori Samira S, Elias Guilherme, Réus Gislaine Z, Steckert Amanda V, de Souza Bruna, Petronilho Fabrícia, Gavioli Elaine C, Dal-Pizzol Felipe, Quevedo João
Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
Neurochem Int. 2009 Dec;55(7):491-5. doi: 10.1016/j.neuint.2009.05.003. Epub 2009 May 15.
The intracerebroventricular (ICV) administration of ouabain (a Na(+)/K(+)-ATPase inhibitor) in rats has been suggested to mimic some symptoms of human bipolar mania. Clinical studies have shown that bipolar disorder may be related to mitochondrial dysfunction. Herein, we investigated the behavioral and biochemical effects induced by the ICV administration of ouabain in rats. To achieve this aim, the effects of ouabain injection immediately after and 7 days following a single ICV administration (at concentrations of 10(-2) and 10(-3)M) on locomotion was measured using the open-field test. Additionally, thiobarbituric acid reactive substances (TBARSs) and superoxide production were measured in submitochondrial particles of the prefrontal cortex, hippocampus, striatum and amygdala. Our findings demonstrated that ouabain at 10(-2) and 10(-3)M induced hyperlocomotion in rats, and this response remained up to 7 days following a single ICV injection. In addition, we observed that the persistent increase in the rat spontaneous locomotion is associated with increased TBARS levels and superoxide generation in submitochondrial particles in the prefrontal cortex, striatum and amygdala. In conclusion, ouabain-induced mania-like behavior may provide a useful animal model to test the hypothesis of the involvement of oxidative stress in bipolar disorder.
在大鼠中，脑室内（ICV）注射哇巴因（一种钠钾ATP酶抑制剂）被认为可模拟人类双相躁狂症的某些症状。临床研究表明，双相情感障碍可能与线粒体功能障碍有关。在此，我们研究了脑室内注射哇巴因对大鼠行为和生化方面的影响。为实现这一目标，使用旷场试验测量了单次脑室内注射（浓度为10⁻²和10⁻³M）后立即以及7天后注射哇巴因对运动的影响。此外，还测量了前额叶皮质、海马体、纹状体和杏仁核亚线粒体颗粒中的硫代巴比妥酸反应性物质（TBARSs）和超氧化物生成量。我们的研究结果表明，10⁻²和10⁻³M的哇巴因可诱导大鼠运动亢进，且这种反应在单次脑室内注射后可持续7天。此外，我们观察到大鼠自发运动的持续增加与前额叶皮质、纹状体和杏仁核亚线粒体颗粒中TBARS水平升高和超氧化物生成增加有关。总之，哇巴因诱导的躁狂样行为可能为检验氧化应激参与双相情感障碍这一假说提供有用的动物模型。
