Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity
Journal of Neuroscience August 1, 1988 Elizabeth O’hearn, Giuseppe Battaglia, Eb de Souza et al. 546 citations
Two amphetamine derivatives, MDA and MDMA, cause lasting damage to serotonin-producing nerve fibers in the rat brain. Two weeks after repeated high doses, serotonin axons throughout the forebrain are profoundly lost, while dopamine and norepinephrine axons remain intact. The damage is selective to fine axon terminals; thicker fibers and the cell bodies in the raphe nuclei survive. Some brain regions, such as the hippocampus and parts of the neocortex, show partial sparing. Swollen and fragmented axons observed shortly after treatment confirm ongoing degeneration. MDA produces greater loss of serotonin axons than MDMA at the same dose. The findings establish that these drugs are toxic to serotonin axon terminals and cause long-term denervation of the forebrain.