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Schmidt CJ. 
“Acute and long-term neurochemical effects of methylenedioxymethamphetamine in the rat”. 
NIDA Res Monogr. 1989;94:179-95.
Administration of a single dose of methylenedioxymethamphetamine (MDMA) to rats at doses above 10 mg/kg produces a biphasic pattern of serotonin (5-HT) depletion in the central nervous system (CNS) shown for the cerebral cortex in Figure 1. Much of the work on MDMA in our laboratory has involved the characterization of these two phases of transmitter depletion following MDMA. Our results indicate that these two periods of depletion are unique with respect to their mechanism, timecourse, and stereochemical requirements. The acute effect of MDMA, which is maximal between 3 and 6 hours following drug administration, involves a disruption of 5-HT synthesis coupled with an increase in transmitter turnover. These early effects of MDMA on the serotonergic neuron appear to be ultimately reversible. The second phase of depletion develops several days after the administration of MDMA and is associated with a decrease in the number of serotonergic nerve terminals. It is the latter decrease in transmitter concentrations that corresponds to the neurotoxic effect of MDMA. Attempts have been made to compare these in vivo effects of MDMA with some of its in vitro activities to gain insight into the mechanism(s) responsible for the complex neurochemical response elicited by this drug.
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