Acute and long-term effects of MDMA on cerebral dopamine biochemistry and function.
OBJECTIVE
The majority of experimental and clinical studies on the pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) tend to focus on its action on 5-HT biochemistry and function. However, there is considerable evidence for MDMA having marked acute effects on dopamine release. Furthermore, while MDMA produces long-term effects on 5-HT neurones in most species examined, in mice its long-term effects appear to be restricted to the dopamine system. The objective of this review is to examine the actions of MDMA on dopamine biochemistry and function in mice, rats, guinea pigs, monkeys and humans.


CONCLUSIONS
MDMA appears to produce a major release of dopamine from its nerve endings in all species investigated. This release plays a significant role in the expression of many of the behaviours that occur, including behavioural changes, alterations of the mental state in humans and the potentially life-threatening hyperthermia that can occur. While MDMA appears to be a selective 5-HT neurotoxin in most species examined (rats, guinea pigs and primates), it is a selective dopamine neurotoxin in mice. Selectivity may be a consequence of what neurotoxic metabolites are produced (which may depend on dosing schedules), their selectivity for monoamine nerve endings, or the endogenous free radical trapping ability of specific nerve endings, or both. We suggest more focus be made on the actions of MDMA on dopamine neurochemistry and function to provide a better understanding of the acute and long-term consequences of using this popular recreational drug.
Colado
M Isabel
MI
Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense, 28040 Madrid, Spain. colado@med.ucm.es
O'Shea
Esther
E
Green
A Richard
AR
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D006213:Hallucinogens / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D013045:Species Specificity
D006213:Hallucinogens; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine