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

Abstract In the last years our research group has studied and validated the animal model of mania induced by dextroamphetamine ( d -AMPH). Considering the lack of animal models of mania reported in the literature; this study evaluated the possibilities to validate the animal model induced by methamphetamine (m-AMPH). Then, we evaluated the effects of lithium (Li), valproate (VPA) on the behavior and parameters of oxidative damage in rat brain after administration of m-AMPH. In the prevention treatment, Wistar rats were pretreated with Li, VPA or saline (Sal) for 14 days, and then, between days 8 and 14, rats were treated with m-AMPH (1, 0.5 or 0.25 mg/kg) or Sal. In the reversal treatment, rats were first given m-AMPH (0.25 mg/kg) or Sal. Locomotor behavior was assessed using the open-field task and parameters of oxidative damage were measured in brain structures. Our results show that the hyperactivity was prevented and reverted by Li and VPA only when m-AMPH was administered in the dose of 0.25 mg/kg. In addition, the m-AMPH in all doses administrated induced oxidative damage in both structures tested in two models. Li and VPA reversed and prevented this impairment, however in a way dependent of cerebral area, the dose of m-AMPH and technique.