The effects of presence, versus absence, of a functioning noradrenergic (norepinephrine-related) system on severity of MDMA neurotoxicity was studied in mice. Saline-treated controls and animals given the noradrenergic neurotoxin DSP-4 received 3 doses of saline or 30 mg/kg MDMA every 2 h, 3 days after DSP-4 or saline. Mice were killed 1 week after MDMA. Striatal catecholamines (dopamine and norepinephrine) were assessed via HPLC in one group of mice, and in another group, the researchers assessed striatal dopamine neurons via electron microscope and immunocytochemical staining with anti-ubiquitin and anti-heat shock protein. (In mice, MDMA neurotoxicity affects dopamine, and not serotonin, neurons). MDMA produced greater reduction in striatal dopamine in mice given DSP-4 than in mice with intact noradrenergic function. Ultrastructural whorls positive for ubiquitin were observed in the cytosol and nuclei of striatal dopamine cells in mice given MDMA alone or after DSP-4 pretreatment. (DSP-4 lesioning itself may have produced whorls in striatal dopamine cells as well). Study findings suggest that DMA neurotoxicity is intensified when the noradrenergic system is also damaged. Since MDMA neurotoxicity seen in non-human primates is similar to effects seen in rats, and not mice, it is not clear whether reduced noradrenergic function increases risk or scope of long-term effects of ecstasy use in humans. In a previous report, Fornai and colleagues (Fornai et al. 2002) described finding ultrastructural whorls in striatal cells in mice given MDMA.