Intracerebroventricular (ICV) injection of ouabain (a potent Na(+)/K(+)-ATPase inhibitor) in rats resulted in manic-like effects. There is an emerging body of data indicating that major neuropsychiatric disorders, such as bipolar disorder and schizophrenia, are associated with increased oxidative stress. In this study, we investigated the effects of ICV ouabain injection on oxidative stress parameters in total tissue of rat brain. Our findings demonstrated that ICV injection increased thiobarbituric acid reactive species levels and protein carbonyl generation in the prefrontal cortex and hippocampus of rats. Moreover, the activity of the antioxidants enzymes catalase and superoxide dismutase was altered in several areas of the rat brain and cerebrospinal fluid of ICV ouabain-subjected rats. These results showed that Na(+)/K(+)-ATPase inhibition can lead to oxidative stress in the brain of rats.