title: Effects of tamoxifen on tricarboxylic acid cycle enzymes in the brain of rats submitted to an animal model of mania induced by amphetamine.
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 dysfunction seen in BD, and TMX exert protective effects against the d-AMPH-induced TCA cycle enzymes dysfunction.
authors.affiliation: Laboratory of Neurosciences, National Institute for Translational Medicine (INCT-TM), Postgraduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, 88806-000 Criciúma, SC, Brazil.
authors.forename: Samira S
authors.initials: SS
authors.lastname: Valvassori
authors.affiliation: Laboratory of Neurosciences, National Institute for Translational Medicine (INCT-TM), Postgraduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, 88806-000 Criciúma, SC, Brazil.
authors.forename: Daniela V
authors.initials: DV
authors.lastname: Bavaresco
authors.affiliation: Laboratory of Neurosciences, National Institute for Translational Medicine (INCT-TM), Postgraduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, 88806-000 Criciúma, SC, Brazil.
authors.forename: Josiane
authors.initials: J
authors.lastname: Budni
authors.affiliation: Laboratory of Neurosciences, National Institute for Translational Medicine (INCT-TM), Postgraduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, 88806-000 Criciúma, SC, Brazil.
authors.forename: Tamara S
authors.initials: TS
authors.lastname: Bobsin
authors.affiliation: Laboratory of Bioenergetics, National Institute for Translational Medicine (INCT-TM), Postgraduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, 88806-000, Brazil.
authors.forename: Cinara L
authors.initials: CL
authors.lastname: Gonçalves
authors.affiliation: Laboratory of Bioenergetics, National Institute for Translational Medicine (INCT-TM), Postgraduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, 88806-000, Brazil.
authors.forename: Karolina V
authors.initials: KV
authors.lastname: de Freitas
authors.affiliation: Laboratory of Bioenergetics, National Institute for Translational Medicine (INCT-TM), Postgraduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, 88806-000, Brazil.
authors.forename: Emilio L
authors.initials: EL
authors.lastname: Streck
authors.affiliation: Laboratory of Neurosciences, National Institute for Translational Medicine (INCT-TM), Postgraduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, 88806-000 Criciúma, SC, Brazil. Electronic address: quevedo@unesc.net.
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
mesh_terms: D000661:Amphetamine; D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002952:Citric Acid Cycle / Q000187:drug effects*; D004195:Disease Models, Animal; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013629:Tamoxifen / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D018692:Antimanic Agents; D013629:Tamoxifen; D000661:Amphetamine
keywords: Amphetamine; Citrate synthase; Malate dehydrogenase; Succinate dehydrogenase; Tamoxifen