The neurobiological basis of
bipolar disorder (BD) remains unknown; nevertheless,
mitochondrial dysfunction has been identified in this disorder. Inactivation of any step in the
tricarboxylic acid (TCA) cycle can impair mitochondrial
ATP production. There is recent evidence indicating that PKC is an important therapeutic target for
bipolar disorder. Therefore, we evaluated the effects of
tamoxifen (TMX--a PKC inhibitor) on the activities of
enzymes in the TCA cycle of rat brains subjected to an animal model of
mania induced by
amphetamine. In the reversal treatment, Wistar rats were first treated with d-AMPH or saliratsne (Sal) for 14 days. Thereafter, between days 8 and 14, the rats were administered TMX or Sal. The
citrate synthase,
succinate dehydrogenase, and
malate dehydrogenase were evaluated in the frontal cortex, hippocampus, and striatum. The d-AMPH administration inhibited TCA cycle
enzymes activity in all analyzed structures, and TMX reversed d-AMPH-induced dysfunction. In addition, we observed a negative correlation between d-AMPH-induced hyperactivity and the activity of these
enzymes in the rat's brain. These findings suggested that TCA cycle
enzymes inhibition can be an important link for the
mitochondrial dysfunction seen in BD, and TMX exert protective effects against the d-AMPH-induced TCA cycle
enzymes dysfunction.