Researchers altered dietary selenium as a means of investigating the role of oxidative stress in MDMA neurotoxicity in mice and (Dark Agouti) rats. The researchers assessed cortical, striatal and hippocampal serotonin and dopamine levels, and degree of radiolabelled paroxetine binding, a measure of serotonin function, in both species. Animals were fed a selenium-deficient (< 0.02 ppm) or selenium-augmented (replete) diet (0.2 ppm) for 8 weeks, and received MDMA or saline 7 weeks after the start of the study, and all animals were killed 7 days after they received MDMA. Mice received 3 doses of 15 mg/kg MDMA or saline, with injections given every 3 h, and rats received a single injection of saline or 12.5 mg/kg MDMA. Not only did the selenium-deficient diet exacerbate MDMA-associated reduction in striatal dopamine and metabolites in mice, it also reduced serotonin and metabolites in mouse hippocampus, striatum and cortex. In contrast, a selenium-deficient diet neither enhanced nor attenuated reduction in serotonin and metabolites after MDMA in rats, and it did not produce any changes in levels of brain dopamine or dopamine metabolites. It is important to note that mice fed a selenium-deficient diet also lost weight, while rat body weight was unaffected by amount of dietary selenium. Levels of dietary selenium did not significantly alter MDMA-induced hyperthermia in either mice or rats. Measures of glutathione peroxidase (GPx) activity and lipid peroxidase activity (measures of oxidative stress) in mouse cortex and striatum found 30% reduction in GPx activity in both areas, and higher cortical lipid peroxidation in selenium-deficient mice. In rats, a selenium-deficient diet did reduce cortical, striatal and hippocampal GPx activity, though it did not produce greater lipid peroxidation in rat cortex or striatum. (Studies of oxidative stress in the same brain regions of mice and rats consuming a standard diet indicate that mice, but not rats, have lower cortical GPX activity and higher striatal peroxidation). The authors conclude that MDMA-induced dopamine neurotoxicity in mice is due to oxidative stress, and that MDMA-induced oxidative stress is modest in rats. However, while they present a model for mouse MDMA neurotoxicity based on previous research, they do not propose a model of MDMA neurotoxicity in rats. Along with findings also reported by the same research team (Colado et al. 2002), the current findings demonstrate differences in mechanisms of MDMA neurotoxicity in mice and rats. However, it should be noted that Dark Agouti rats were employed in this study rather than a more commonly studied rat strain, such as Sprague-Dawley or Wistar, and it is possible that findings in the Dark Agouti strain may not generalize to other strains. Rats and primates may either share similar metabolic pathways or similar means of dealing with oxidative stress, affects on serotonin axons, and not dopamine axons. If humans are assumed to be more similar to the rats in this study, then findings suggest that increasing selenium intake is unlikely to be neuroprotective in human ecstasy users.