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Schmidt CJ, Kehne JH.
“Neurotoxicity of MDMA: neurochemical effects”.
Ann N Y Acad Sci. 1990;600:665-80; discussion 6.
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Abstract
3,4-Methylenedioxymethamphetamine (MDMA) is one of several amphetamines which can damage serotonergic nerve terminals when administered at high doses to laboratory animals. A single injection of MDMA produces a characteristic biphasic pattern of 5-HT depletion in the rat brain. Remarkably similar patterns are observed following the administration of p-chloroamphetamine (PCA), methamphetamine (METH) or methylenedioxyamphetamine (MDA) to rats. In our studies we have designated these two phases of 5-HT depletion as the acute or reversible phase and the long-term or neurotoxic phase. The acute neurochemical effects of MDMA begin immediately after drug administration with a rapid decline in the activity of the rate-limiting enzyme for 5-HT synthesis, tryptophan hydroxylase (TPH). During this same period there is an increase in carrier-mediated efflux of 5-HT which is believed to be responsible for the behavioral effects of MDMA. The increase in transmitter release coupled with the inhibition of synthesis results in a significant reduction in brain 5-HT concentrations during the first 3-6 h after drug administration. By 6 h there is a decline in the behavioral effects of MDMA as stransmitter elfflux ceases. Although TPH activity remains depressed, this is followed by a gradual recovery of 5-HT concentrations over the next 12 hours. The neurotoxic effects of MDMA appear between 24h and 1 week after drug administration. By 7 days, this second decrease in 5-HT concentrations is associated with a loss of functional 5-HT uptake sites indicating damage to serotonergic nerve terminals.
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