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Acute methylenedioxymethamphetamine administration: effects on local cerebral blood flow and glucose utilisation in the dark agouti rat

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Abstract

Rationale

Clinical reports indicate that acute exposure to 3,4-methylenedioxymethamphetamine (MDMA; “Ecstasy”) may induce pathological cerebrovascular responses in human users of the drug, however, the mechanism by which MDMA might effect these pathological changes is not clear.

Objectives

To examine the effects of acute MDMA administration on the relationship between local cerebral blood flow (LCBF) and local cerebral glucose utilisation (LCMRglu); to determine the effect, if any, acute exposure to MDMA has on the cerebral circulation, independently of alterations in cerebral metabolic demand.

Methods

Dark Agouti rats were injected with 15 mg.kg−1 i.p. MDMA or saline equivalent. LCBF and LCMRglu were measured in 50 brain areas using the fully quantitative [14C]iodoantipyrine and [14C]2-deoxyglucose autoradiographic techniques, respectively.

Results

MDMA produced significant increases in LCMRglu in 23 brain areas, most markedly in the motor system (globus pallidus; +82%; medial striatum; +71%). In contrast, significant decreases in LCBF were observed in 28 brain areas, most markedly in primary sensory nuclei (superior colliculus; −32%) and limbic areas (anterior thalamus; −34%). Global analysis revealed a close correlation (r=0.87) between LCMRglu and LCBF with a ratio of 1.53 in controls. Despite the divergence of LCMRglu (increases) and LCBF (decreases) in MDMA-treated groups, there was a similar close correlation (r=0.84), but the ratio was decreased to 1.22.

Conclusions

This study provides clear evidence that acute exposure to MDMA results in cerebrovascular dysfunction. The uncoupling of LCBF from underlying metabolic demand, possibly due to the vasoconstrictor action of 5-HT, could provide the basis for oligaemia-induced pathological changes in the brain.

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Acknowledgements

This study was funded by EC grant no. QLG3-CT-2002–00809, and by the Wellcome Trust.

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Authors and Affiliations

  1. School of Health Sciences, Queen Margaret University College, Edinburgh, EH12 8TS, UK

    Linda Quate & Douglas E. McBean

  2. Division of Clinical Neuroscience, University of Edinburgh, 1 George Square, Edinburgh, EH8 9JZ, UK

    Isobel M. Ritchie, Henry J. Olverman & Paul A. T. Kelly

Authors
  1. Linda Quate
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  2. Douglas E. McBean
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  3. Isobel M. Ritchie
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  4. Henry J. Olverman
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  5. Paul A. T. Kelly
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Correspondence to Paul A. T. Kelly.

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Quate, L., McBean, D.E., Ritchie, I.M. et al. Acute methylenedioxymethamphetamine administration: effects on local cerebral blood flow and glucose utilisation in the dark agouti rat. Psychopharmacology 173, 287–295 (2004). https://doi.org/10.1007/s00213-004-1784-z

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  • DOI: https://doi.org/10.1007/s00213-004-1784-z

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