Effects of ouabain on cytokine/chemokine levels in an animal model of mania.

Bipolar disorder (BD) is a chronic and severe psychiatric disorder and despite its importance, little is known about the precise pathophysiology of this disorder. Several studies have reported that inflammation plays a role in the pathogenesis of BD and that cytokines are altered in these patients. Intracerebroventricular (ICV) injection of ouabain (a potent Na(+)/K(+)-ATPase inhibitor) in rats resulted in manic-like effects and it has been widely used as an animal model of bipolar mania. In this study, we assessed the cytokine levels (IL-1β, IL-6, IL-10, TNF-α, CINC-1) in the brain structures (hippocampus, striatum, frontal cortex, amygdala), serum and cerebrospinal fluid (CSF) of rats submitted to an animal model of mania induced by ouabain. Our findings demonstrated that ouabain induced hyperlocomotion in rats. However, the only cytokine that showed alteration was IL-6, which was decreased in the striatum after ouabain administration. In conclusion, despite the ouabain administration in rats be a valid model to study the physiopathology of bipolar mania, it seems that this model was not able to mimic the changes in cytokines observed in bipolar patients.