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Effects of alpha-lipoic acid in an animal model of mania induced by D-amphetamine.

Abstract

OBJECTIVES

Oxidative stress and neurotrophic factors are involved in the pathophysiology of bipolar disorder (BD). Alpha-lipoic acid (ALA) is a naturally occurring compound with strong antioxidant properties. The present study investigated ALA effects in an amphetamine-induced model of mania.

METHODS

In the reversal protocol, adult mice were first given d-amphetamine (AMPH) 2 mg/kg, intraperitoneally (i.p.) or saline for 14 days. Between days 8 and 14, the animals received ALA 50 or 100 mg/kg orally, lithium (Li) 47.5 mg/kg i.p., or saline. In the prevention paradigm, mice were pretreated with ALA, Li, or saline prior to AMPH. Locomotor activity was assessed in the open-field task. Superoxide dismutase (SOD) activity, reduced glutathione (GSH), and thiobarbituric acid-reactive substance (TBARS) levels were evaluated in the prefrontal cortex (PFC), hippocampus (HC), and striatum (ST). Brain-derived neurotrophic factor (BDNF) levels were measured in the HC.

RESULTS

ALA and Li prevented and reversed the AMPH-induced increase in locomotor activity. PREVENTION MODEL: ALA and Li co-administration with AMPH prevented the decrease in SOD activity induced by AMPH in the HC and ST, respectively; ALA and Li prevented GSH alteration in the HC and TBARS formation in all brain areas studied. REVERSAL MODEL: ALA reversed the decrease in SOD activity in the ST. TBARS formation was reversed by ALA and Li in all brain areas. Furthermore, ALA reversed AMPH-induced decreases in BDNF and GSH in the HC.

CONCLUSIONS

Our findings showed that ALA, similarly to Li, is effective in reversing and preventing AMPH-induced behavioral and neurochemical alterations, providing a rationale for the design of clinical trials investigating ALA's possible antimanic effect.

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  • Authors+Show Affiliations

    ,

    Neuropharmacology Laboratory, Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Ceará, Brazil.

    , , , , , , , ,

    Source

    Bipolar disorders 14:7 2012 Nov pg 707-18

    MeSH

    Animals
    Antimanic Agents
    Bipolar Disorder
    Brain
    Brain-Derived Neurotrophic Factor
    Central Nervous System Stimulants
    Dextroamphetamine
    Disease Models, Animal
    Dose-Response Relationship, Drug
    Drug Administration Schedule
    Glutathione
    Lipid Peroxidation
    Lithium Chloride
    Male
    Malondialdehyde
    Mice
    Motor Activity
    Superoxide Dismutase
    Thiobarbituric Acid Reactive Substances
    Thioctic Acid

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    22897629

    Citation

    Macêdo, Danielle S., et al. "Effects of Alpha-lipoic Acid in an Animal Model of Mania Induced By D-amphetamine." Bipolar Disorders, vol. 14, no. 7, 2012, pp. 707-18.
    Macêdo DS, Medeiros CD, Cordeiro RC, et al. Effects of alpha-lipoic acid in an animal model of mania induced by D-amphetamine. Bipolar Disord. 2012;14(7):707-18.
    Macêdo, D. S., Medeiros, C. D., Cordeiro, R. C., Sousa, F. C., Santos, J. V., Morais, T. A., ... Carvalho, A. F. (2012). Effects of alpha-lipoic acid in an animal model of mania induced by D-amphetamine. Bipolar Disorders, 14(7), pp. 707-18. doi:10.1111/j.1399-5618.2012.01046.x.
    Macêdo DS, et al. Effects of Alpha-lipoic Acid in an Animal Model of Mania Induced By D-amphetamine. Bipolar Disord. 2012;14(7):707-18. PubMed PMID: 22897629.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Effects of alpha-lipoic acid in an animal model of mania induced by D-amphetamine. AU - Macêdo,Danielle S, AU - Medeiros,Camila D, AU - Cordeiro,Rafaela C, AU - Sousa,Francisca Cléa, AU - Santos,Júnia V, AU - Morais,Thomás A, AU - Hyphantis,Thomas N, AU - McIntyre,Roger S, AU - Quevedo,João, AU - Carvalho,André F, Y1 - 2012/08/17/ PY - 2012/8/18/entrez PY - 2012/8/18/pubmed PY - 2013/4/20/medline SP - 707 EP - 18 JF - Bipolar disorders JO - Bipolar Disord VL - 14 IS - 7 N2 - OBJECTIVES: Oxidative stress and neurotrophic factors are involved in the pathophysiology of bipolar disorder (BD). Alpha-lipoic acid (ALA) is a naturally occurring compound with strong antioxidant properties. The present study investigated ALA effects in an amphetamine-induced model of mania. METHODS: In the reversal protocol, adult mice were first given d-amphetamine (AMPH) 2 mg/kg, intraperitoneally (i.p.) or saline for 14 days. Between days 8 and 14, the animals received ALA 50 or 100 mg/kg orally, lithium (Li) 47.5 mg/kg i.p., or saline. In the prevention paradigm, mice were pretreated with ALA, Li, or saline prior to AMPH. Locomotor activity was assessed in the open-field task. Superoxide dismutase (SOD) activity, reduced glutathione (GSH), and thiobarbituric acid-reactive substance (TBARS) levels were evaluated in the prefrontal cortex (PFC), hippocampus (HC), and striatum (ST). Brain-derived neurotrophic factor (BDNF) levels were measured in the HC. RESULTS: ALA and Li prevented and reversed the AMPH-induced increase in locomotor activity. PREVENTION MODEL: ALA and Li co-administration with AMPH prevented the decrease in SOD activity induced by AMPH in the HC and ST, respectively; ALA and Li prevented GSH alteration in the HC and TBARS formation in all brain areas studied. REVERSAL MODEL: ALA reversed the decrease in SOD activity in the ST. TBARS formation was reversed by ALA and Li in all brain areas. Furthermore, ALA reversed AMPH-induced decreases in BDNF and GSH in the HC. CONCLUSIONS: Our findings showed that ALA, similarly to Li, is effective in reversing and preventing AMPH-induced behavioral and neurochemical alterations, providing a rationale for the design of clinical trials investigating ALA's possible antimanic effect. SN - 1399-5618 UR - https://www.unboundmedicine.com/medline/citation/22897629/Effects_of_alpha_lipoic_acid_in_an_animal_model_of_mania_induced_by_D_amphetamine_ L2 - https://doi.org/10.1111/j.1399-5618.2012.01046.x DB - PRIME DP - Unbound Medicine ER -