Effects of tamoxifen on tricarboxylic acid cycle enzymes in the brain of rats submitted to an animal model of mania induced by amphetamine

Psychiatry Research
Samira S ValvassoriJoão Quevedo

Abstract

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 dysfun...Continue Reading

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Citations

Nov 8, 2015·Progress in Neuro-psychopharmacology & Biological Psychiatry·Ajaykumar N SharmaJoao Quevedo
Oct 23, 2016·Free Radical Biology & Medicine·Luiz K S KanazawaRoberto Andreatini
Mar 17, 2017·Journal of Cellular Physiology·Josef VečeřaStanislav Kozubek
Mar 19, 2021·Frontiers in Behavioral Neuroscience·Luiz Arthur Rangel CyrinoThayná Patachini Maia

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