title: Lithium and valproate modulate energy metabolism in an animal model of mania induced by methamphetamine.
abstract: Studies have shown alterations in mitochondrial complexes of bipolar disorder (BD) patients. However, changes in the Krebs cycle enzymes have been little studied. The animal model of mania induced by amphetamine has been widely used for the study of bipolar mania. The aim of this study is to assess behavioral and energy metabolism changes in an animal model of mania induced by methamphetamine (m-AMPH). Wistar rats were first given m-AMPH or saline for 14 days, and then, between days 8 and 14, rats were treated with lithium (Li), valproate (VPA), or saline (Sal). Locomotor behavior was assessed using the open-field task and activities of Krebs cycle enzymes (citrate synthase and succinate dehydrogenase), mitochondrial respiratory chain complexes (I, II, III, and IV), and creatine kinase measured in the brain structures (prefrontal, amygdala, hippocampus, and striatum). Li and VPA reversed m-AMPH-induced hyperactivity. The administration of m-AMPH inhibited the activities of Krebs cycle enzymes and complexes of the mitochondrial respiratory chain in all analyzed structures. Li and VPA reversed m-AMPH-induced energetic metabolism dysfunction; however, the effects of Li and VPA were dependent on the brain region analyzed. From the results obtained in this study, we suggested that the decreased Krebs cycle enzymes activity induced by m-AMPH may be inhibiting mitochondrial respiratory chain complexes. Therefore, changes in the Krebs cycle enzymes may also be involved in BD.
authors.affiliation: Laboratory of Neurosciences, National Institute for Translational Medicine, and Center of Excellence in Applied Neurosciences of Santa Catarina, Postgraduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, 88806-000 Criciúma, SC, Brazil.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Feier
authors.forename: Samira S
authors.initials: SS
authors.lastname: Valvassori
authors.forename: Roger B
authors.initials: RB
authors.lastname: Varela
authors.forename: Wilson R
authors.initials: WR
authors.lastname: Resende
authors.forename: Daniela V
authors.initials: DV
authors.lastname: Bavaresco
authors.forename: Meline O
authors.initials: MO
authors.lastname: Morais
authors.forename: Giselli
authors.initials: G
authors.lastname: Scaini
authors.forename: Monica L
authors.initials: ML
authors.lastname: Andersen
authors.forename: Emilio L
authors.initials: EL
authors.lastname: Streck
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
mesh_terms: D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000139:chemically induced* / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002952:Citric Acid Cycle / Q000187:drug effects; D003402:Creatine Kinase / Q000378:metabolism; D004195:Disease Models, Animal; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects*; D018020:Lithium Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014635:Valproic Acid / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D018692:Antimanic Agents; D045222:Electron Transport Chain Complex Proteins; D018020:Lithium Compounds; D008694:Methamphetamine; D014635:Valproic Acid; D003402:Creatine Kinase