Researchers sought evidence of MDMA-induced neuronal degeneration in rats by examining brain slices with Fluoro-Jade B staining. Rats received a single dose of saline or MDMA (10, 20 or 40 mg/kg), and were then killed 3 days post-drug. Selected brain regions were examined, including parietal and insular cortex, tenia tecta, ventromedial, paraventricular and intralaminar thalamus, and bed nucleus of the stria terminalis. All animals receiving 20 or 40 mg/kg MDMA showed some indicators of neuronal degeneration, whereas only one rat receiving 10 mg/kg MDMA showed any signs of neuronal degeneration (in parietal cortex, tenia tecta and ventromedial thalamus). Signs of neuronal degeneration were seen in these and additional areas in rats given higher doses, including thalamic areas and (in one animal) insula after 20 mg/kg, and all areas examined in two or more rats after 40 mg/kg. Increased signs of neuronal degeneration were closely linked with increased body temperature, as the only rat with signs of hyperthermia after 10 mg/kg MDMA was also the only one to exhibit increased Fluoro-Jade B staining. The authors state that most areas exhibiting signs of neuronal degeneration are densely innervated by monoaminergic axons, but do not differentiate between monoamines. This is not the first report of MDMA neurotoxicity unrelated to serotonin axons (Commins et al. 1987; Fornai et al. 2002, in mice), but it is the first report of extensive neuronal degeneration. Differences in rat ages, times from drug administration to sacrifice, or ambient temperature may be responsible for findings of greater degeneration in this study. Hyperthermia appears to be associated with increased Fluoro-Jade B staining after MDMA, and it may be that hyperthermia is necessary for causing apparent neuronal degeneration. To date, similar findings in primates have not been reported, and contrary to the authors’ assertions, humans are very likely to be less prone to MDMA-induced hyperthermia than rodents, as hyperthermia remains a rare event in humans (see Henry and Rella 2001). Hence the relevance of these findings for humans is uncertain.