title: Fenproporex increases locomotor activity and alters energy metabolism, and mood stabilizers reverse these changes: a proposal for a new animal model of mania.
abstract: Fenproporex (Fen) is converted in vivo into amphetamine, which is used to induce mania-like behaviors in animals. In the present study, we intend to present a new animal model of mania. In order to prove through face, construct, and predictive validities, we evaluated behavioral parameters (locomotor activity, stereotypy activity, and fecal boli amount) and brain energy metabolism (enzymes citrate synthase; malate dehydrogenase; succinate dehydrogenase; complexes I, II, II-III, and IV of the mitochondrial respiratory chain; and creatine kinase) in rats submitted to acute and chronic administration of fenproporex, treated with lithium (Li) and valproate (VPA). The administration of Fen increased locomotor activity and decreased the activity of Krebs cycle enzymes, mitochondrial respiratory chain complexes, and creatine kinase, in most brain structures evaluated. In addition, treatment with mood stabilizers prevented and reversed this effect. Our results are consistent with the literature that demonstrates behavioral changes and mitochondrial dysfunction caused by psychostimulants. These findings suggest that chronic administration of Fen may be a potential animal model of mania.
authors.affiliation: Laboratório de Bioenergética e Núcleo de Excelência em Neurociências Aplicadas de Santa Catarina (NENASC), Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
authors.forename: Gislaine T
authors.initials: GT
authors.lastname: Rezin
authors.forename: Camila B
authors.initials: CB
authors.lastname: Furlanetto
authors.forename: Giselli
authors.initials: G
authors.lastname: Scaini
authors.forename: Samira S
authors.initials: SS
authors.lastname: Valvassori
authors.forename: Cinara L
authors.initials: CL
authors.lastname: Gonçalves
authors.forename: Gabriela K
authors.initials: GK
authors.lastname: Ferreira
authors.forename: Isabela C
authors.initials: IC
authors.lastname: Jeremias
authors.forename: Wilson R
authors.initials: WR
authors.lastname: Resende
authors.forename: Mariane R
authors.initials: MR
authors.lastname: Cardoso
authors.forename: Roger B
authors.initials: RB
authors.lastname: Varela
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
authors.forename: Emilio L
authors.initials: EL
authors.lastname: Streck
mesh_terms: D000662:Amphetamines / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D008094:Lithium / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014635:Valproic Acid / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000662:Amphetamines; D018692:Antimanic Agents; D014635:Valproic Acid; D008094:Lithium; C026013:fenproporex