High doses of MDMA (ecstasy) reduce serotonin levels in the brains of rats, but this reduction does not necessarily indicate that neurons have been damaged. The drug works by stimulating the release of serotonin, norepinephrine, and dopamine. At doses that cause long-term serotonin depletion (10-20 mg/kg), markers of actual neuronal damage such as cell death or gliosis are not reliably increased. Even moderate doses that do not deplete serotonin can produce lasting anxiety-like behaviors in rats, suggesting potential risks from the drug beyond neurotoxicity.
Two weeks after giving rats MDMA (7.5 mg/kg, three doses) or the toxin 5,7-DHT, the study measured serotonin levels and two protein markers in brain regions. MDMA reduced tissue serotonin by about 50% in cortex, hippocampus, and caudate but did not significantly change the amount of serotonin transporter or glial fibrillary acidic protein, a marker of nerve damage. In contrast, 5,7-DHT reduced serotonin by over 90%, lowered serotonin transporter protein by 20–35%, and increased glial fibrillary acidic protein by 30–39%. The authors conclude that this MDMA regimen does not cause degeneration of serotonin nerve terminals and that lasting serotonin depletion can occur without destroying the axons.