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Effects of mood stabilizers on mitochondrial respiratory chain activity in brain of rats treated with d-amphetamine.

Abstract

Bipolar disorder (BD) is a devastating major mental illness associated with high rates of suicide and work loss. There is an emerging body of data suggesting that bipolar disorder is associated with mitochondrial dysfunction. In this context, the present study aims to investigate the effects of mood stabilizers lithium (Li) and valproate (VPT) on mitochondrial respiratory chain activity in brain of rats undergoing treatment with the pro-manic agent d-AMPH d-amphetamine (d-AMPH). In the reversal treatment, Wistar rats were first given d-AMPH or saline for 14 days, and then, between days 8 and 14, rats were treated with Li, VPA or saline (Sal). In the prevention treatment, rats were pretreated with Li, VPA or Sal. Locomotor behavior was assessed using the open-field task and mitochondrial chain activity complexes I, II, III and IV were measured in brain structures (hippocampus, striatum and prefrontal). Li and VPA reversed and prevented d-AMPH-induced hyperactivity. In both experiments, d-AMPH inhibited mitochondrial respiratory chain activity in all analyzed structures. In the reversal treatment, VPA reversed d-AMPH-induced dysfunction in all brain regions analyzed. In the prevention experiment, the effects of Li and VPA on d-AMPH-induced mitochondrial dysfunction were dependent on the brain region analyzed. These findings suggested that dopamine can be an important link for the mitochondrial dysfunction seen in BD and, Li and VPA exert protective effects against this d-AMPH-induced mitochondrial dysfunction, but this effect varies depending on the brain region and the treatment regimen.

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  • Authors+Show Affiliations

    ,

    Laboratory of Neurosciences and National Institute for Translational Medicine, Postgraduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, 88806-000 Criciúma, SC, Brazil.

    , , , , , , ,

    Source

    Journal of psychiatric research 44:14 2010 Oct pg 903-9

    MeSH

    Animals
    Antimanic Agents
    Bipolar Disorder
    Brain
    Corpus Striatum
    Dextroamphetamine
    Disease Models, Animal
    Dopamine Uptake Inhibitors
    Electron Transport
    Electron Transport Complex I
    Electron Transport Complex II
    Electron Transport Complex III
    Electron Transport Complex IV
    Hippocampus
    Lithium Compounds
    Locomotion
    Male
    Mitochondria
    Motor Activity
    Prefrontal Cortex
    Rats
    Rats, Wistar
    Valproic Acid

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    20334877

    Citation

    Valvassori, Samira S., et al. "Effects of Mood Stabilizers On Mitochondrial Respiratory Chain Activity in Brain of Rats Treated With D-amphetamine." Journal of Psychiatric Research, vol. 44, no. 14, 2010, pp. 903-9.
    Valvassori SS, Rezin GT, Ferreira CL, et al. Effects of mood stabilizers on mitochondrial respiratory chain activity in brain of rats treated with d-amphetamine. J Psychiatr Res. 2010;44(14):903-9.
    Valvassori, S. S., Rezin, G. T., Ferreira, C. L., Moretti, M., Gonçalves, C. L., Cardoso, M. R., ... Quevedo, J. (2010). Effects of mood stabilizers on mitochondrial respiratory chain activity in brain of rats treated with d-amphetamine. Journal of Psychiatric Research, 44(14), pp. 903-9. doi:10.1016/j.jpsychires.2010.02.009.
    Valvassori SS, et al. Effects of Mood Stabilizers On Mitochondrial Respiratory Chain Activity in Brain of Rats Treated With D-amphetamine. J Psychiatr Res. 2010;44(14):903-9. PubMed PMID: 20334877.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Effects of mood stabilizers on mitochondrial respiratory chain activity in brain of rats treated with d-amphetamine. AU - Valvassori,Samira S, AU - Rezin,Gislaine T, AU - Ferreira,Camila L, AU - Moretti,Morgana, AU - Gonçalves,Cinara L, AU - Cardoso,Mariana R, AU - Streck,Emílio L, AU - Kapczinski,Flávio, AU - Quevedo,João, Y1 - 2010/03/23/ PY - 2009/12/07/received PY - 2010/02/01/revised PY - 2010/02/02/accepted PY - 2010/3/26/entrez PY - 2010/3/26/pubmed PY - 2011/2/3/medline SP - 903 EP - 9 JF - Journal of psychiatric research JO - J Psychiatr Res VL - 44 IS - 14 N2 - Bipolar disorder (BD) is a devastating major mental illness associated with high rates of suicide and work loss. There is an emerging body of data suggesting that bipolar disorder is associated with mitochondrial dysfunction. In this context, the present study aims to investigate the effects of mood stabilizers lithium (Li) and valproate (VPT) on mitochondrial respiratory chain activity in brain of rats undergoing treatment with the pro-manic agent d-AMPH d-amphetamine (d-AMPH). In the reversal treatment, Wistar rats were first given d-AMPH or saline for 14 days, and then, between days 8 and 14, rats were treated with Li, VPA or saline (Sal). In the prevention treatment, rats were pretreated with Li, VPA or Sal. Locomotor behavior was assessed using the open-field task and mitochondrial chain activity complexes I, II, III and IV were measured in brain structures (hippocampus, striatum and prefrontal). Li and VPA reversed and prevented d-AMPH-induced hyperactivity. In both experiments, d-AMPH inhibited mitochondrial respiratory chain activity in all analyzed structures. In the reversal treatment, VPA reversed d-AMPH-induced dysfunction in all brain regions analyzed. In the prevention experiment, the effects of Li and VPA on d-AMPH-induced mitochondrial dysfunction were dependent on the brain region analyzed. These findings suggested that dopamine can be an important link for the mitochondrial dysfunction seen in BD and, Li and VPA exert protective effects against this d-AMPH-induced mitochondrial dysfunction, but this effect varies depending on the brain region and the treatment regimen. SN - 1879-1379 UR - https://www.unboundmedicine.com/medline/citation/20334877/Effects_of_mood_stabilizers_on_mitochondrial_respiratory_chain_activity_in_brain_of_rats_treated_with_d_amphetamine_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-3956(10)00050-6 DB - PRIME DP - Unbound Medicine ER -