MDMA (ecstasy) causes lasting damage to the brain's serotonin system. In Dark Agouti rats, a single injection of MDMA at doses of 7.5, 15, or 30 mg/kg reduced the density of serotonin-producing axons throughout the brain 3 and 7 days later. Three days after treatment, a dose-dependent increase in the stress protein Hsp27 appeared in star-shaped glial cells (astrocytes) in several cortical areas and the hippocampus CA1 region, but not in other brain regions like the caudate putamen. The hippocampus CA1 showed both increased Hsp27 and another marker of glial activation (GFAP), suggesting particular vulnerability. High-dose MDMA also triggered Hsp72 in neurons, indicating effects beyond serotonin cells.
A single dose of MDMA (15 mg/kg) in male Dark Agouti rats caused lasting damage to the serotonin system, shown by 30–60% reductions in paroxetine binding in the forebrain and decreased brain glucose metabolism in aggression-related areas. Despite this neurotoxicity, aggressive behaviors (biting, boxing, wrestling) were not significantly different from controls three weeks later, and the acute anti-aggressive effects of MDMA and two 5-HT1B receptor agonists remained intact. The findings suggest that aggressive behavior and the acute anti-aggressive action of MDMA are preserved even with substantial serotonergic damage, at least under the social isolation conditions of the resident-intruder test.