Older mice (10-week-old) given a neurotoxic regimen of MDMA showed greater hyperthermia and more severe dopaminergic damage than younger mice (4-week-old). Seven days after treatment, older animals had significant reductions in vesicular monoamine transporter 2 (37%) and tyrosine hydroxylase (58%), while younger animals did not. Dopamine transporter expression dropped in both age groups (26% in younger, 69.7% in older), and striatal dopamine and its metabolite were lower in both, with older animals more affected. The findings indicate age-related susceptibility to MDMA-induced neurotoxicity.
Rats that voluntarily self-administered moderate doses of MDMA (approximately 2.0–7.0 mg/kg/day) over 20 daily 2-hour sessions initially showed a drop in core body temperature after each session compared to baseline and to a control group that self-administered saline. Over time, this hypothermic response diminished, and by the final sessions core temperatures had risen above baseline. Locomotor activity during MDMA sessions was initially similar to saline levels but became significantly greater by day 8. These findings demonstrate that repeated voluntary MDMA intake leads to experience-dependent changes in temperature regulation and behavior.