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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.
AuthorsGislaine T Rezin, Camila B Furlanetto, Giselli Scaini, Samira S Valvassori, Cinara L Gonçalves, Gabriela K Ferreira, Isabela C Jeremias, Wilson R Resende, Mariane R Cardoso, Roger B Varela, João Quevedo, Emilio L Streck
JournalMolecular neurobiology (Mol Neurobiol) Vol. 49 Issue 2 Pg. 877-92 (Apr 2014) ISSN: 1559-1182 [Electronic] United States
PMID24126971 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Amphetamines
  • Antimanic Agents
  • Valproic Acid
  • Lithium
  • fenproporex
Topics
  • Amphetamines (pharmacology, therapeutic use)
  • Animals
  • Antimanic Agents (pharmacology, therapeutic use)
  • Bipolar Disorder (drug therapy, metabolism)
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Energy Metabolism (drug effects, physiology)
  • Lithium (pharmacology, therapeutic use)
  • Male
  • Motor Activity (drug effects, physiology)
  • Rats
  • Rats, Wistar
  • Valproic Acid (pharmacology, therapeutic use)

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