THE EFFECTS OF METHYLENEDIOXYMETHAMPHETAMINE (MDMA, ECSTASY) ON MONOAMINERGIC NEUROTRANSMISSION IN THE CENTRAL-NERVOUS-SYSTEM

Methylenedioxymethamphetamine (MDMA, Ecstasy) is a popular recreationa lly used drug among young people in Europe and North America. The rece nt surge in use of MDMA and increasing concerns about possible toxic e ffects of the drug have inspired a great deal of research into the mec hanisms by which the drug may affect the central nervous system. This paper reviews studies on the neurochemical, behavioral and neurophysio logical effects of MDMA, with emphasis on MDMA effects in regions of t he brain that have been implicated in reward. Experiments in awake, be having laboratory animals have demonstrated that single injections of MDMA increase extracellular levels of the neurotransmitters dopamine ( DA) and serotonin (5HT) in the nucleus accumbens and in several other brain regions that are important for reward. Most of the behavioral an d electrophysiological changes that have been reported to date for sin gle doses of MDMA appear to be mediated by this MDMA-induced increase in extracellular DA and 5HT. As an example, MDMA-induced hyperthermia and locomotor hyperactivity in laboratory animals can be blocked by ad ministering drugs that prevent MDMA-induced 5HT release and can be att enuated by administering 5HT receptor antagonists, whereas effects of MDMA on delayed reinforcement tasks appear to be mediated by MDMA-indu ced increases in extracellular DA. Similarly, the effects of MDMA on n euronal excitability in the nucleus accumbens and in several other bra in regions can be prevented by administering drugs that block MDMA-ind uced 5HT release and can be attenuated by depleting brain DA levels or by administering either DA D-1 receptor antagonists or 5HT receptor a ntagonists. In addition to the acute effects of MDMA, it is now well e stablished that repeated or high-dose administration of MDMA is neurot oxic to a subpopulation of 5HT-containing axons that project to the fo rebrain in laboratory animals. Recent studies have shown that this neu rotoxic effect of MDMA is associated with long-duration changes in bot h DA and 5HT neurotransmission in the nucleus accumbens. Whether these long-duration changes in neurotransmission might be related to report s of depression and other psychopathologies by some frequent users of MDMA remains to be determined. Methylenedioxymethamphetamine has been found to increase extracellular levels of norepinephrine and to alter brain levels of several neuropeptides as well as altering levels of DA and 5HT. Much additional research is required to understand the multi ple ways in which this complex drug may alter neurotransmission in the brain, both acutely and in the long term. Copyright (C) 1996 Elsevier Science Ltd.