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Effects of mood stabilizers on hippocampus and amygdala BDNF levels in an animal model of mania induced by ouabain.

Abstract

There is a body of evidence suggesting that BDNF is involved in bipolar disorder (BD) pathogenesis. Intracerebroventricular (ICV) injection of ouabain (OUA), a specific Na(+)/K(+) ATPase inhibitor, induces hyperlocomotion in rats, and has been used as an animal model of mania. The present study aims to investigate the effects of the lithium (Li) and valproate (VPT) in an animal model of mania induced by ouabain. In the reversal model, animals received a single ICV injection of OUA or cerebrospinal fluid (aCSF). From the day following the ICV injection, the rats were treated for 6 days with intraperitoneal (IP) injections of saline (SAL), Li or VPT twice a day. In the maintenance treatment (prevention model), the rats received IP injections of Li, VPT, or SAL twice a day for 12 days. In the 7th day of treatment the animals received a single ICV injection of either OUA or aCSF. After the ICV injection, the treatment with the mood stabilizers continued for more 6 days. Locomotor activity was measured using the open-field test and BDNF levels were measured in rat hippocampus and amygdala by sandwich-ELISA. Li and VPT reversed OUA-related hyperactive behavior in the open-field test in both experiments. OUA decreased BDNF levels in first and second experiments in hippocampus and amygdala and Li treatment, but not VPT reversed and prevented the impairment in BDNF expression after OUA administration in these cerebral areas. Our results suggest that the present model fulfills adequate face, construct and predictive validity as an animal model of mania.

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  • Authors+Show Affiliations

    ,

    Laboratory of Neurosciences and National Science and Technology Institute for Translational Medicine, Postgraduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, 88808-000 Criciúma, SC, Brazil.

    , , , , , , ,

    Source

    Journal of psychiatric research 44:8 2010 Jun pg 506-10

    MeSH

    Amygdala
    Analysis of Variance
    Animals
    Antimanic Agents
    Bipolar Disorder
    Brain-Derived Neurotrophic Factor
    Disease Models, Animal
    Drug Interactions
    Enzyme-Linked Immunosorbent Assay
    Gene Expression Regulation
    Hippocampus
    Lithium Chloride
    Male
    Motor Activity
    Ouabain
    Rats
    Rats, Wistar
    Valproic Acid

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    19954800

    Citation

    Jornada, Luciano K., et al. "Effects of Mood Stabilizers On Hippocampus and Amygdala BDNF Levels in an Animal Model of Mania Induced By Ouabain." Journal of Psychiatric Research, vol. 44, no. 8, 2010, pp. 506-10.
    Jornada LK, Moretti M, Valvassori SS, et al. Effects of mood stabilizers on hippocampus and amygdala BDNF levels in an animal model of mania induced by ouabain. J Psychiatr Res. 2010;44(8):506-10.
    Jornada, L. K., Moretti, M., Valvassori, S. S., Ferreira, C. L., Padilha, P. T., Arent, C. O., ... Quevedo, J. (2010). Effects of mood stabilizers on hippocampus and amygdala BDNF levels in an animal model of mania induced by ouabain. Journal of Psychiatric Research, 44(8), pp. 506-10. doi:10.1016/j.jpsychires.2009.11.002.
    Jornada LK, et al. Effects of Mood Stabilizers On Hippocampus and Amygdala BDNF Levels in an Animal Model of Mania Induced By Ouabain. J Psychiatr Res. 2010;44(8):506-10. PubMed PMID: 19954800.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Effects of mood stabilizers on hippocampus and amygdala BDNF levels in an animal model of mania induced by ouabain. AU - Jornada,Luciano K, AU - Moretti,Morgana, AU - Valvassori,Samira S, AU - Ferreira,Camila L, AU - Padilha,Peterson T, AU - Arent,Camila O, AU - Fries,Gabriel R, AU - Kapczinski,Flavio, AU - Quevedo,João, Y1 - 2009/12/01/ PY - 2009/09/17/received PY - 2009/10/29/revised PY - 2009/11/03/accepted PY - 2009/12/4/entrez PY - 2009/12/4/pubmed PY - 2010/8/13/medline SP - 506 EP - 10 JF - Journal of psychiatric research JO - J Psychiatr Res VL - 44 IS - 8 N2 - There is a body of evidence suggesting that BDNF is involved in bipolar disorder (BD) pathogenesis. Intracerebroventricular (ICV) injection of ouabain (OUA), a specific Na(+)/K(+) ATPase inhibitor, induces hyperlocomotion in rats, and has been used as an animal model of mania. The present study aims to investigate the effects of the lithium (Li) and valproate (VPT) in an animal model of mania induced by ouabain. In the reversal model, animals received a single ICV injection of OUA or cerebrospinal fluid (aCSF). From the day following the ICV injection, the rats were treated for 6 days with intraperitoneal (IP) injections of saline (SAL), Li or VPT twice a day. In the maintenance treatment (prevention model), the rats received IP injections of Li, VPT, or SAL twice a day for 12 days. In the 7th day of treatment the animals received a single ICV injection of either OUA or aCSF. After the ICV injection, the treatment with the mood stabilizers continued for more 6 days. Locomotor activity was measured using the open-field test and BDNF levels were measured in rat hippocampus and amygdala by sandwich-ELISA. Li and VPT reversed OUA-related hyperactive behavior in the open-field test in both experiments. OUA decreased BDNF levels in first and second experiments in hippocampus and amygdala and Li treatment, but not VPT reversed and prevented the impairment in BDNF expression after OUA administration in these cerebral areas. Our results suggest that the present model fulfills adequate face, construct and predictive validity as an animal model of mania. SN - 1879-1379 UR - https://www.unboundmedicine.com/medline/citation/19954800/Effects_of_mood_stabilizers_on_hippocampus_and_amygdala_BDNF_levels_in_an_animal_model_of_mania_induced_by_ouabain_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-3956(09)00254-4 DB - PRIME DP - Unbound Medicine ER -