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Effects of lithium and valproate on oxidative stress and behavioral changes induced by administration of m-AMPH

Dayane D da-Rosa1, Samira S Valvassori, Amanda V Steckert

  • 1Laboratory 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.

Psychiatry Research
|March 21, 2012
PubMed

Insights

This study validates methamphetamine (m-AMPH) as a mania model in rats. Lithium (Li) and valproate (VPA) effectively reversed m-AMPH-induced hyperactivity and oxidative damage, particularly at lower doses.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Biochemistry

Background:

  • The development of reliable animal models for mania is crucial for understanding and treating bipolar disorder.
  • Existing models, such as dextroamphetamine-induced mania, have limitations.
  • Methamphetamine (m-AMPH) presents a potential alternative for inducing manic-like behaviors and associated neurochemical changes.

Purpose of the Study:

  • To validate methamphetamine (m-AMPH) as an animal model of mania.
  • To investigate the efficacy of lithium (Li) and valproate (VPA) in preventing and reversing m-AMPH-induced behavioral and oxidative stress parameters.
  • To assess the dose-dependency and regional specificity of m-AMPH effects and the therapeutic actions of Li and VPA.

Main Methods:

  • Wistar rats were subjected to prevention and reversal treatment paradigms.
  • Locomotor activity was measured using the open-field task.
  • Oxidative damage markers were analyzed in specific rat brain structures following m-AMPH administration.
  • Animals were pretreated or post-treated with Li, VPA, or saline before/after m-AMPH exposure.

Main Results:

  • Methamphetamine (m-AMPH) administration induced hyperactivity and oxidative damage in rat brains across all tested doses.
  • Lithium (Li) and valproate (VPA) demonstrated efficacy in preventing and reversing hyperactivity and oxidative damage, but this effect was most pronounced at the lowest m-AMPH dose (0.25 mg/kg).
  • The neuroprotective effects of Li and VPA were dependent on the specific brain region, m-AMPH dose, and treatment strategy.

Conclusions:

  • Methamphetamine (m-AMPH) serves as a valid animal model for mania, inducing behavioral and biochemical alterations relevant to the disorder.
  • Lithium (Li) and valproate (VPA) show therapeutic potential in mitigating m-AMPH-induced mania-like symptoms and neurotoxicity.
  • Further research is warranted to elucidate the precise mechanisms and optimize treatment strategies based on dose and brain region specificity.

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