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Acute and long-term effects of MDMA on cerebral dopamine biochemistry and function

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Abstract

Rationale and objectives

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.

Results and discussion

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.

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Acknowledgement

We thank all the colleagues who we have had the pleasure of working with on MDMA over the years. M.I.C. thanks Plan Nacional sobre Drogas (Ministerio del Interior), Ministerio de Ciencia y Tecnologia (SAF2001-1437), Ministerio de Sanidad (FIS01/0844; FIS G03/005) and Fundacion MapfreMedicina for financial support.

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  1. Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense, 28040, Madrid, Spain

    M. Isabel Colado & Esther O’Shea

  2. Neuropharmacology Research Group, School of Pharmacy, De Montfort University, Leicester, LE1 9BH, UK

    A. Richard Green

  3. AstraZeneca R&D Charnwood, Bakewell Road, Loughborough, LE11 5RH, UK

    A. Richard Green

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  1. M. Isabel Colado
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  2. Esther O’Shea
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Correspondence to M. Isabel Colado.

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Colado, M.I., O’Shea, E. & Green, A.R. Acute and long-term effects of MDMA on cerebral dopamine biochemistry and function. Psychopharmacology 173, 249–263 (2004). https://doi.org/10.1007/s00213-004-1788-8

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