title: Fluvoxamine alters the activity of energy metabolism enzymes in the brain.
abstract: OBJECTIVE
  Several studies support the hypothesis that metabolism impairment is involved in the pathophysiology of depression and that some antidepressants act by modulating brain energy metabolism. Thus, we evaluated the activity of Krebs cycle enzymes, the mitochondrial respiratory chain, and creatine kinase in the brain of rats subjected to prolonged administration of fluvoxamine.
  
  
  METHODS
  Wistar rats received daily administration of fluvoxamine in saline (10, 30, and 60 mg/kg) for 14 days. Twelve hours after the last administration, rats were killed by decapitation and the prefrontal cortex, cerebral cortex, hippocampus, striatum, and cerebellum were rapidly isolated.
  
  
  RESULTS
  The activities of citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV were decreased after prolonged administration of fluvoxamine in rats. However, the activities of complex II, succinate dehydrogenase, and creatine kinase were increased.
  
  
  CONCLUSIONS
  Alterations in activity of energy metabolism enzymes were observed in most brain areas analyzed. Thus, we suggest that the decrease in citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV can be related to adverse effects of pharmacotherapy, but long-term molecular adaptations cannot be ruled out. In addition, we demonstrated that these changes varied according to brain structure or biochemical analysis and were not dose-dependent.
authors.affiliation: Bioenergetics Laboratory, Center of Excellence in Applied Neurosciences of Santa Catarina (NENASC), Graduate Program in Health Sciences, Universidade do Extremo Sul Catarinense (UNESC), Criciúma, SC, Brazil.
authors.forename: Gabriela K
authors.initials: GK
authors.lastname: Ferreira
authors.affiliation: Bioenergetics Laboratory, Center of Excellence in Applied Neurosciences of Santa Catarina (NENASC), Graduate Program in Health Sciences, Universidade do Extremo Sul Catarinense (UNESC), Criciúma, SC, Brazil.
authors.forename: Mariane R
authors.initials: MR
authors.lastname: Cardoso
authors.affiliation: Bioenergetics Laboratory, Center of Excellence in Applied Neurosciences of Santa Catarina (NENASC), Graduate Program in Health Sciences, Universidade do Extremo Sul Catarinense (UNESC), Criciúma, SC, Brazil.
authors.forename: Isabela C
authors.initials: IC
authors.lastname: Jeremias
authors.affiliation: Bioenergetics Laboratory, Center of Excellence in Applied Neurosciences of Santa Catarina (NENASC), Graduate Program in Health Sciences, Universidade do Extremo Sul Catarinense (UNESC), Criciúma, SC, Brazil.
authors.forename: Cinara L
authors.initials: CL
authors.lastname: Gonçalves
authors.affiliation: Bioenergetics Laboratory, Center of Excellence in Applied Neurosciences of Santa Catarina (NENASC), Graduate Program in Health Sciences, Universidade do Extremo Sul Catarinense (UNESC), Criciúma, SC, Brazil.
authors.forename: Karolina V
authors.initials: KV
authors.lastname: Freitas
authors.affiliation: Bioenergetics Laboratory, Center of Excellence in Applied Neurosciences of Santa Catarina (NENASC), Graduate Program in Health Sciences, Universidade do Extremo Sul Catarinense (UNESC), Criciúma, SC, Brazil.
authors.forename: Rafaela
authors.initials: R
authors.lastname: Antonini
authors.affiliation: Bioenergetics Laboratory, Center of Excellence in Applied Neurosciences of Santa Catarina (NENASC), Graduate Program in Health Sciences, Universidade do Extremo Sul Catarinense (UNESC), Criciúma, SC, Brazil.
authors.forename: Giselli
authors.initials: G
authors.lastname: Scaini
authors.affiliation: Clinical and Experimental Pathophysiology Laboratory, Graduate Program in Health Sciences, Universidade do Sul de Santa Catarina (UNISUL), Tubarão, SC, Brazil.
authors.forename: Gislaine T
authors.initials: GT
authors.lastname: Rezin
authors.affiliation: National Science and Technology Institute for Translational Medicine (INCT-TM), Porto Alegre, RS, Brazil.
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
authors.affiliation: Bioenergetics Laboratory, Center of Excellence in Applied Neurosciences of Santa Catarina (NENASC), Graduate Program in Health Sciences, Universidade do Extremo Sul Catarinense (UNESC), Criciúma, SC, Brazil.
authors.forename: Emilio L
authors.initials: EL
authors.lastname: Streck
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002952:Citric Acid Cycle / Q000187:drug effects; D003402:Creatine Kinase / Q000187:drug effects; D003866:Depressive Disorder / Q000188:drug therapy; D004579:Electron Transport / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D016666:Fluvoxamine / Q000008:administration & dosage*; D008291:Malate Dehydrogenase / Q000187:drug effects; D008297:Male; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage*
chemical_list: D000928:Antidepressive Agents; D003402:Creatine Kinase; D016666:Fluvoxamine; D008291:Malate Dehydrogenase; D017367:Selective Serotonin Reuptake Inhibitors