Intracerebroventricular ouabain administration induces oxidative stress in the rat brain.

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.

Animal model of mania induced by ouabain: Evidence of oxidative stress in submitochondrial particles of the rat brain.

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.

Inhibition of mitochondrial respiratory chain in brain of rats subjected to an experimental model of depression.

Depressive disorders, including major depression, are serious and disabling. However, the exact pathophysiology of depression is not clearly understood. Life stressors contribute in some fashion to depression and are an extension of what occurs normally. In this context, chronic stress has been used as an animal model of depression. Based on the hypothesis that metabolism impairment might be involved in the pathophysiology of depression, in the present work we evaluated the activities of mitochondrial respiratory chain complexes and creatine kinase in brain of rats subjected to chronic stress. After 40 days of mild stress, a reduction in sweet food ingestion was observed, as well as increased adrenal gland weight, when compared to control group. We also verified that control group gained weight after 40 days, but stressed group did not. Moreover, our findings showed that complex I, III and IV were inhibited in stress group only in cerebral cortex and cerebellum. On the other hand, complex II and creatine kinase were not affected in stressed group. Although it is difficult to extrapolate our findings to the human condition, the inhibition of mitochondrial respiratory chain by chronic stress may be one mechanism in the pathophysiology of depressive disorders.

Comparing validity of Edinburgh scale and SRQ20 in screening for post-partum depression.

The Edinburgh Postnatal Depression Scale (EPDS) is the instrument most used worldwide for screening of Post-Partum Depression (PPD). The SRQ20 questionnaire has been largely used for screening of minor psychiatric disorders. This study aimed to compare the accuracy of the two instruments in screening for PPD. At the third-month follow-up home visit to infants of the 2004 Pelotas Birth Cohort, Southern Brazil, a sub-sample of 378 mothers was selected. Among other questions, EPDS and SRQ20 were applied by trained fieldworkers. Up to 15 days later, a mental health professional re-interviewed the mother (the gold standard interview). Sensitivity and specificity of each cutoff point were calculated for EPDS and SRQ20 and the results were plotted at a ROC curve. The areas under both curves were compared. Highest sensitivity and specificity cutoff were observed for EPDS >/= 10 (sensitivity 82.7%, 95%CI 74.0 - 89.4; specificity 65.3%, 95%CI 59.4 - 71.0) and for SRQ20 >/= 6 (sensitivity 70.5%, 95%CI 60.8 - 79.0%; specificity 75.5%, 95%CI 70.0 - 80.5%). Shape of ROC curves and areas under both curves were virtually identical (respectively, 0.8401 +/- 0.02 for EPDS and 0.8402 +/- 0.02 for SRQ20; p = 0.9). In conclusion SRQ20 showed to be as valid as EPDS as a screening tool for PPD at third month after delivery.