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Effects of lithium on oxidative stress and behavioral alterations induced by lisdexamfetamine dimesylate: relevance as an animal model of mania.

Abstract

Lisdexamfetamine dimesylate (LDX) is a prodrug that requires conversion to d-amphetamine (d-AMPH) for bioactivity. Treatment with d-AMPH induces hyperlocomotion and is regarded as a putative animal model of bipolar mania. Therefore, we sought to determine the behavioral and oxidative stress alterations induced by sub-chronic LDX administration as well as their reversal and prevention by lithium in rats. A significant increment in locomotor behavior was induced by LDX (10 and 30 mg/kg). To determine Li effects against LDX-induced alterations, in the reversal protocol rats received LDX (10 or 30 mg/kg) or saline for 14 days. Between days 8 and 14 animals received Li (47.5 mg/kg, i.p.) or saline. In the prevention paradigm, rats were pretreated with Li or saline prior to LDX administration. Glutathione (GSH) levels and lipid peroxidation was determined in the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST) of rats. Lithium prevented LDX-induced hyperlocomotion at the doses of 10 and 30 mg/kg, but only reversed LDX-induced hyperlocomotion at dose of 10mg/kg. In addition, both doses of LDX decreased GSH content (in ST and PFC), while Li was able to reverse and prevent these alterations mainly in the PFC. LDX (10 and 30 mg/kg) increased lipid peroxidation which was reversed and prevented by Li. In conclusion, LDX-induced hyperlocomotion along with associated increments in oxidative stress show promise as an alternative animal model of mania.

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  • Authors+Show Affiliations

    ,

    Psychiatry Research Group, Federal University of Ceará, Faculty of Medicine, Fortaleza, Ceara, Brazil.

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    Source

    MeSH

    Animals
    Antimanic Agents
    Behavior, Animal
    Bipolar Disorder
    Brain Chemistry
    Central Nervous System Stimulants
    Dextroamphetamine
    Dose-Response Relationship, Drug
    Glutathione
    Hippocampus
    Lipid Peroxidation
    Lisdexamfetamine Dimesylate
    Lithium
    Lithium Carbonate
    Male
    Motor Activity
    Neostriatum
    Oxidative Stress
    Prefrontal Cortex
    Rats
    Rats, Wistar
    Thiobarbituric Acid Reactive Substances

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    23333378

    Citation

    Macêdo, Danielle S., et al. "Effects of Lithium On Oxidative Stress and Behavioral Alterations Induced By Lisdexamfetamine Dimesylate: Relevance as an Animal Model of Mania." Progress in Neuro-psychopharmacology & Biological Psychiatry, vol. 43, 2013, pp. 230-7.
    Macêdo DS, de Lucena DF, Queiroz AI, et al. Effects of lithium on oxidative stress and behavioral alterations induced by lisdexamfetamine dimesylate: relevance as an animal model of mania. Prog Neuropsychopharmacol Biol Psychiatry. 2013;43:230-7.
    Macêdo, D. S., de Lucena, D. F., Queiroz, A. I., Cordeiro, R. C., Araújo, M. M., Sousa, F. C., ... Carvalho, A. F. (2013). Effects of lithium on oxidative stress and behavioral alterations induced by lisdexamfetamine dimesylate: relevance as an animal model of mania. Progress in Neuro-psychopharmacology & Biological Psychiatry, 43, pp. 230-7. doi:10.1016/j.pnpbp.2013.01.007.
    Macêdo DS, et al. Effects of Lithium On Oxidative Stress and Behavioral Alterations Induced By Lisdexamfetamine Dimesylate: Relevance as an Animal Model of Mania. Prog Neuropsychopharmacol Biol Psychiatry. 2013 Jun 3;43:230-7. PubMed PMID: 23333378.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Effects of lithium on oxidative stress and behavioral alterations induced by lisdexamfetamine dimesylate: relevance as an animal model of mania. AU - Macêdo,Danielle S, AU - de Lucena,David F, AU - Queiroz,Ana Isabelle G, AU - Cordeiro,Rafaela C, AU - Araújo,Maíra M, AU - Sousa,Francisca Cléa, AU - Vasconcelos,Silvânia M, AU - Hyphantis,Thomas N, AU - Quevedo,João, AU - McIntyre,Roger S, AU - Carvalho,André F, Y1 - 2013/01/17/ PY - 2012/09/20/received PY - 2012/12/19/revised PY - 2013/01/10/accepted PY - 2013/1/22/entrez PY - 2013/1/22/pubmed PY - 2013/9/21/medline SP - 230 EP - 7 JF - Progress in neuro-psychopharmacology & biological psychiatry JO - Prog. Neuropsychopharmacol. Biol. Psychiatry VL - 43 N2 - Lisdexamfetamine dimesylate (LDX) is a prodrug that requires conversion to d-amphetamine (d-AMPH) for bioactivity. Treatment with d-AMPH induces hyperlocomotion and is regarded as a putative animal model of bipolar mania. Therefore, we sought to determine the behavioral and oxidative stress alterations induced by sub-chronic LDX administration as well as their reversal and prevention by lithium in rats. A significant increment in locomotor behavior was induced by LDX (10 and 30 mg/kg). To determine Li effects against LDX-induced alterations, in the reversal protocol rats received LDX (10 or 30 mg/kg) or saline for 14 days. Between days 8 and 14 animals received Li (47.5 mg/kg, i.p.) or saline. In the prevention paradigm, rats were pretreated with Li or saline prior to LDX administration. Glutathione (GSH) levels and lipid peroxidation was determined in the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST) of rats. Lithium prevented LDX-induced hyperlocomotion at the doses of 10 and 30 mg/kg, but only reversed LDX-induced hyperlocomotion at dose of 10mg/kg. In addition, both doses of LDX decreased GSH content (in ST and PFC), while Li was able to reverse and prevent these alterations mainly in the PFC. LDX (10 and 30 mg/kg) increased lipid peroxidation which was reversed and prevented by Li. In conclusion, LDX-induced hyperlocomotion along with associated increments in oxidative stress show promise as an alternative animal model of mania. SN - 1878-4216 UR - https://www.unboundmedicine.com/medline/citation/23333378/Effects_of_lithium_on_oxidative_stress_and_behavioral_alterations_induced_by_lisdexamfetamine_dimesylate:_relevance_as_an_animal_model_of_mania_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0278-5846(13)00009-2 DB - PRIME DP - Unbound Medicine ER -