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

Authors

  • Danielle S Macêdo,

    1. Neuropharmacology Laboratory, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
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  • Camila D Medeiros,

    1. Neuropharmacology Laboratory, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
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  • Rafaela C Cordeiro,

    1. Neuropharmacology Laboratory, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
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  • Francisca Cléa Sousa,

    1. Neuropharmacology Laboratory, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
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  • Júnia V Santos,

    1. Neuropharmacology Laboratory, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
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  • Thomás A Morais,

    1. Neuropharmacology Laboratory, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
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  • Thomas N Hyphantis,

    1. Department of Psychiatry, School of Medicine, University of Ioannina, Ioannina, Greece
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  • Roger S McIntyre,

    1. Department of Psychiatry, University of Toronto
    2. Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada
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  • João Quevedo,

    1. Laboratory of Neurosciences and National Institute for Translational Medicine (INCT-TM), Postgraduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma
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  • André F Carvalho

    1. Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
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  • Part of this research was presented in poster form at the 24th European College of Neuropsychopharmacology Congress, 3–7 September 2011, Paris, France.

Corresponding author:
André F Carvalho, M.D., Ph.D.
Department of Clinical Medicine
Faculty of Medicine
Federal University of Ceará
Rua Prof. Costa Mendes, 1608, 4oandar
Fortaleza
CE 60430-040
Brazil
Fax: +55-85-32617227
E-mail: andrefc7@terra.com.br

Abstract

Macêdo DS, Medeiros CD, Cordeiro RC, Sousa FC, Santos JV, Morais TA, Hyphantis TN, McIntyre RS, Quevedo J, Carvalho AF. Effects of alpha-lipoic acid in an animal model of mania induced by d-amphetamine. Bipolar Disord 2012: 14: 707–718. © 2012 The Authors.
Journal compilation © 2012 John Wiley & Sons A/S

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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