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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.

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  • Authors+Show Affiliations

    ,

    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.

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    Source

    MeSH

    Animals
    Antimanic Agents
    Bipolar Disorder
    Brain
    Citric Acid Cycle
    Creatine Kinase
    Disease Models, Animal
    Electron Transport Chain Complex Proteins
    Energy Metabolism
    Lithium Compounds
    Male
    Methamphetamine
    Motor Activity
    Rats
    Rats, Wistar
    Valproic Acid

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    23010382

    Citation

    Feier, Gustavo, et al. "Lithium and Valproate Modulate Energy Metabolism in an Animal Model of Mania Induced By Methamphetamine." Pharmacology, Biochemistry, and Behavior, vol. 103, no. 3, 2013, pp. 589-96.
    Feier G, Valvassori SS, Varela RB, et al. Lithium and valproate modulate energy metabolism in an animal model of mania induced by methamphetamine. Pharmacol Biochem Behav. 2013;103(3):589-96.
    Feier, G., Valvassori, S. S., Varela, R. B., Resende, W. R., Bavaresco, D. V., Morais, M. O., ... Quevedo, J. (2013). Lithium and valproate modulate energy metabolism in an animal model of mania induced by methamphetamine. Pharmacology, Biochemistry, and Behavior, 103(3), pp. 589-96. doi:10.1016/j.pbb.2012.09.010.
    Feier G, et al. Lithium and Valproate Modulate Energy Metabolism in an Animal Model of Mania Induced By Methamphetamine. Pharmacol Biochem Behav. 2013;103(3):589-96. PubMed PMID: 23010382.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Lithium and valproate modulate energy metabolism in an animal model of mania induced by methamphetamine. AU - Feier,Gustavo, AU - Valvassori,Samira S, AU - Varela,Roger B, AU - Resende,Wilson R, AU - Bavaresco,Daniela V, AU - Morais,Meline O, AU - Scaini,Giselli, AU - Andersen,Monica L, AU - Streck,Emilio L, AU - Quevedo,João, Y1 - 2012/09/23/ PY - 2012/07/16/received PY - 2012/09/07/revised PY - 2012/09/16/accepted PY - 2012/9/27/entrez PY - 2012/9/27/pubmed PY - 2013/7/10/medline SP - 589 EP - 96 JF - Pharmacology, biochemistry, and behavior JO - Pharmacol. Biochem. Behav. VL - 103 IS - 3 N2 - 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. SN - 1873-5177 UR - https://www.unboundmedicine.com/medline/citation/23010382/Lithium_and_valproate_modulate_energy_metabolism_in_an_animal_model_of_mania_induced_by_methamphetamine_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-3057(12)00268-7 DB - PRIME DP - Unbound Medicine ER -