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Bipolar disorder (BD) is a mental illness associated with higher rates of suicide. The present study aims to investigate the brain mitochondrial respiratory chain activity in an animal model of mania induced by ouabain.Adult male Wistar rats received a single intracerebroventricular administration of ouabain (10−3 and 10−2 M) or vehicle. Locomotor activity was measured using the open field test. Mitochondrial respiratory chain activity was measured in the brain of rats 1 h and 7 days after ouabain administration.Our results showed that spontaneous locomotion was increased 1 h and 7 days after ouabain administration. Complexes I, III and IV activities were increased in the prefrontal cortex, hippocampus and striatum immediately after the administration of ouabain, at the concentration of 10−3 and 10−2 M. Moreover, complex II activity was increased only in the prefrontal cortex at the concentration of 10−2 M. On the other hand, no significant alterations were observed in complex I activity 7 days after ouabain administration. However, an increase in complexes II, III and IV activities was observed only in the prefrontal cortex at the concentration of 10−2 M.Our findings suggest an increase in the activities of mitochondrial respiratory chain in this model of mania. A possible explanation is that these findings occur as a rebound effect trying to compensate for a decrease of ATP deprivation in BD. The present findings suggest that this model may present good face validity and a limitation in construct validity.Freitas TP, Rezin GT, Fraga DB, Moretti M, Vieira JS, Gomes LM, Borges LS, Valvassori SS, Quevedo J, Streck EL. Mitochondrial respiratory chain activity in an animal model of mania induced by ouabain.