Differences between dextroamphetamine and methamphetamine: behavioral changes and oxidative damage in brain of Wistar rats.

In this study methamphetamine (m-AMPH) and dextroamphetamine (d-AMPH) were compared to determine the potency of the two drugs on behavior and oxidative damage in brain of rats. Male adult Wistar rats were given single (acute administration) or repeated (chronic administration, 14 days) intraperitoneal injections of saline (0.9% NaCl), d-AMPH (2 mg/kg) or m-AMPH (0.25, 0.5, 1 or 2 mg/kg). Locomotor activity was evaluated in open-field apparatus 2 h after the last drug injection. Additionally, thiobarbituric acid reactive substances (TBARS) and protein carbonyl formation were measured in the prefrontal cortex, amygdala, hippocampus and striatum. In both experiments, d-AMPH and m-AMPH (all doses administered) increased the locomotor activity of animals, meantime, no significant difference between d-AMPH and m-AMPH was observed. d-AMPH and m-AMPH increased lipid and protein damage, but m-AMPH was more potent than d-AMPH, however, this effect varies depending on the brain region and the experimental protocol. The results of this study show that d-AMPH and m-AMPH have similar behavioral effects, which previous studies had already reported. On the other hand, this study demonstrated that the m-AMPH induces oxidative damage greater than d-AMPH, showing neurochemical differences previously unknown.

Depressive-like behavior accompanies neuroinflammation in an animal model of bipolar disorder symptoms induced by ouabain.

INTRODUCTION: A previous study from our Laboratory showed no alteration in inflammatory parameters seven days after ouabain (OUA) administration, a Na+K+ATPase inhibitor, which was previously considered only a mania model. However, the administration of OUA in rats was recently validated as a model of bipolar disorder (BD) symptoms, demonstrating that 14 days after single intracerebroventricular (ICV) administration, OUA also induces depressive-like behavior. Therefore, it is important to investigate the long-term effect of OUA on inflammatory parameters since this mechanism seems to play a key role in BD physiopathology. METHODS: Adult male Wistar rats received a single ICV administration of OUA or artificial cerebrospinal fluid (aCSF). From the fourth day after the ICV infusion, the rats received saline or Lithium (Li) for 14 days. The open-field test was performed on the 7th day after OUA. On the 14th day, locomotion was re-evaluated, and the forced swimming test (FST) was used to evaluate depressive-like behavior. Inflammatory parameters were assessed in the frontal cortex and hippocampus. RESULTS: OUA increased the locomotion of rats after seven days, considered a mania-like behavior. In the FST, OUA increased the time of immobility on the 14th day, considered a depressive-like behavior. Li reversed the mania-like behavior and partially reversed the depressive-like behavior. Furthermore, OUA increased the levels of interleukin (IL)-1ß, IL-6, IL-10, TNF-α, and CINC-1 in the frontal cortex and hippocampus. Li treatment reverses all these inflammatory alterations. CONCLUSION: This study suggests that the long-term Na+K+ATPase inhibition effects induce depressive-like behavior, which was accompanied by inflammation in the BD symptoms model.

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

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 0.25mg/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.