The effects of a repeated-dose regimen of MDMA on dopamine and serotonin function were studied in squirrel monkeys and baboons. In both studies, animals were given 2 mg/kg MDMA (s.c. in monkeys and i.m. in baboons) or saline every 3 h for a total dose of 9 mg/kg in 6 h. In the first study, monkeys were killed 2 weeks post-treatment, and comparisons were made between MDMA-treated monkeys and controls, with the exception of one animal that died after receiving the third dose and another that did not receive all 3 doses due to unsteadiness after the second dose). In the second study, baboons were killed 2 to 8 weeks post-regimen, and comparisons were made between 4 of 5 MDMA-treated baboons, as 1/5 died after receiving 2 of 3 doses. In both studies, levels of serotonin (5HT), the serotonin metabolite 5-HIAA, dopamine (DA) and the dopamine metabolite DOPAC were measured in brain tissue. Serotonin and dopamine transporter density was measured with autoradiography with the radioligand Beta-CIT (RTI-55) for serotonin transporter and WIN-35428 for dopamine transporter. Silver staining was used to measure axonal degeneration in a single monkey killed 3.5 days after MDMA or saline treatment, and animals were also assessed for presence of glial fibrillary acidic protein (GFAP). Histological and autoradiographic measures found moderate reductions in 5HT, 5HIAA and serotonin transporter density after 3-dose MDMA regimen, with serotonin transporter density lower in all cortical areas, but with 5-HT and 5HIAA lower in frontal and parietal cortex and caudate and putamen only. DA, DOPAC and dopamine transporter were lower in striatum (caudate, putamen) of MDMA treated animals, and silver staining and assessment of GFAP also found these markers of axonal damage in MDMA-treated monkeys. Reduction in dopamine neurons was more severe than serotonin neurons. Findings in baboons were similar except that reductions in 5-HT and 5HIAA were less severe after MDMA treatment (lower 5-HT in caudate and putamen only, lower 5HIAA in putamen, frontal and parietal cortex only). Reduction in markers of dopamine function (DA, DOPAC and dopamine transporter) were lower in MDMA-treated baboons. (Silver staining and GFAP assessment was not performed). Lastly, a separate study examined motor behavior in 3 squirrel monkeys given the dopamine depleter AMPT 1 week before and 1 week after the same 3-dose MDMA regimen. Monkeys were more sensitive to the motor effects of AMPT after receiving MDMA than before treatment. The authors conclude that unlike higher-dose regimens used in other studies in non-human primates, lower-dose regimens damage both dopamine and serotonin axons. They suggest that recreational ecstasy use may increase the risk of developing Parkinson's disease. While assessment of damage to neurons was thorough and included measurements of several markers of degenerating neurons, it is strange that both monkeys and baboons received the same dose regimen. Using the same dose regimen for both species suggests that the authors were not attending to potential effects of interspecies scaling, a model they use later in the paper to support generalizing their findings to human ecstasy users. The mortality rate for both species after receiving this dose seems high in comparison with the relatively low rate of mortality in humans (Gore 1999; Henry and Rella 2001), implying that the doses used in these studies were not equivalent those commonly used by humans. Lastly, previously published studies that assessed DA transporter density in ecstasy users, including a post mortem study of a heavy user, failed to find any indications of damage to dopamine neurons. Hence generalizing study findings to humans seems premature and possibly inappropriate. Nevertheless, these findings, if replicated, may merit attention, particularly if they indicate species-specific or dose-specific drug effects.