Increased oxidative stress after repeated amphetamine exposure: possible relevance as a model of mania

Background: Acute mania can be modeled in animals using D-amphetamine (AMPH). Acute AMPH injections are associated with monoamine depletion, loss of neurofilaments and neurite degeneration. However, the precise mechanisms underlying AMPH-induced neurotoxicity are still unclear. Several studies have demonstrated that oxidative stress may play a role in the behavioral and neurochemical changes observed after AMPH administration. Methods: The effects of a single and repeated injections (seven daily injections) of AMPH administered intraperitonially on locomotion and the production of lipid and protein oxidative markers in rat cortex, striatum and hippocampus were assessed. Locomotion was assessed in an open-field task and markers of oxidative stress were assessed in brain tissue. Results: Both single and repeated injections of AMPH increased protein carbonyl formation in rat brain. Repeated exposure to AMPH induced an additional increase in thiobarbituric acid reactive species in brain tissue. Conclusions: Longer periods of exposure to AMPH were associated with increased oxidative stress in rat brain. This adds to the notion that repeated manic episodes may be associated with greater brain damage and, therefore, poorer outcomes.