Neurotoxic Effects of MDMA on Brain Serotonin Neurons: Evidence from Neurochemical and Radioligand Binding Studiesa

MDMA (ecstasy) causes widespread and long-lasting degeneration of serotonin neurons in the brain, while catecholamine neurons remain largely unaffected. The severity of damage depends on dose, with rhesus monkeys more sensitive than rats. Although serotonin uptake sites can recover over up to a year, functional recovery may be permanently impaired, as serotonin content remains 40–50% below that of age-matched controls even one year after administration. Regional differences in damage are observed, with greater reductions in serotonin uptake sites in brain regions containing terminals, while areas with axons and cell bodies are relatively spared.

Study at a glance

Abstract

In summary, the data from both neurochemical and neuroanatomical studies demonstrate widespread and long-lasting degeneration of serotonin neurons in brain without any major or consistent effects on catecholamine neurons following in vivo administration of MDMA in both rats and rhesus monkeys. A detailed examination of the parameters involved in the neurotoxic and neurodegenerative effects of MDMA on brain serotonin neurons indicate that the severity of the lesion is dependent on the dose of drug administered with the drug being more potent in rhesus monkeys than in rats. Furthermore, the neurodegenerative effects of the drug are long-lasting (up to one year) with respect to neuronal regeneration (i.e. recovery of serotonin uptake sites) while functional recovery may be permanently impaired since serotonin content remains markedly (40-50%) below levels in age-matched controls for as long as one year after drug administration. The neurochemical and autoradiographic data suggest that there are some regional differences and morphological specificity to the neurodegenerative effects of MDMA as demonstrated by greater reductions in serotonin uptake sites in brain regions containing primarily terminals while regions containing axons of passage and cell bodies are relatively unaffected.