Persistent cerebrovascular effects of MDMA and acute responses to the drug

Linda Ferrington, Eszter Kirilly, Douglas E. McBean, Henry J. Olverman, G. Bagdy, Paul A T Kelly

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Acutely, 3,4,-methylenedioxymethamphetamine (MDMA) induces cerebrovascular dysfunction [Quate et al., (2004) Psychopharmacol., 173, 287-295]. In the longer term the same single dose results in depletion of 5-hydroxytrptamine (5-HT) nerve terminals. In this study we examined the cerebrovascular consequences of this persistent neurodegeneration, and the acute effects of subsequent MDMA exposure, upon the relationship that normally exists between local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCMRglu). Dark agouti (DA) rats were pre-treated with 15 mg/kg i.p. MDMA or saline. Three weeks later, rats from each pre-treatment group were treated with an acute dose of MDMA (15 mg/kg i.p.) or saline. Quantitative autoradiographic imaging was used to measure LCBF or LCMRglu with [14C]-iodoantipyrine and [14C]-2- deoxyglucose, respectively. Serotonergic terminal depletion was assessed using radioligand binding with [3H]-paroxetine and immunohistochemistry. Three weeks after MDMA pre-treatment there were significant reductions in densities of 5-HT transporter (SERT)-positive fibres (-46%) and [ 3H]-paroxetine binding (-47%). In animals pre-treated with MDMA there were widespread significant decreases in LCMRglu, but no change in LCBF indicating a persistent loss of cerebrovascular constrictor tone. In both pre-treatment groups, acute MDMA produced significant increases in LCMRglu, while LCBF was significantly decreased. In 50% of MDMA-pre-treated rats, random areas of focal hyperaemia indicated a loss of autoregulatory capacity in response to MDMA-induced hypertension. These results suggest that cerebrovascular regulatory dysfunction resulting from acute exposure to MDMA is not diminished by previous exposure, despite a significant depletion in 5-HT terminals. However, there may be a sub-population, or individual circumstances, in which this dysfunction develops into a condition that might predispose to stroke.

Original languageEnglish
Pages (from-to)509-519
Number of pages11
JournalEuropean Journal of Neuroscience
Volume24
Issue number2
DOIs
Publication statusPublished - Jul 2006

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N-Methyl-3,4-methylenedioxyamphetamine
Cerebrovascular Circulation
Pharmaceutical Preparations
Paroxetine
Hyperemia
Deoxyglucose
Therapeutics
Immunohistochemistry
Stroke
Hypertension

Keywords

  • Dark agouti rat
  • Flow-metabolism relationship
  • Local cerebral blood flow
  • Local cerebral glucose utilization
  • Serotonin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Persistent cerebrovascular effects of MDMA and acute responses to the drug. / Ferrington, Linda; Kirilly, Eszter; McBean, Douglas E.; Olverman, Henry J.; Bagdy, G.; Kelly, Paul A T.

In: European Journal of Neuroscience, Vol. 24, No. 2, 07.2006, p. 509-519.

Research output: Contribution to journalArticle

Ferrington, Linda ; Kirilly, Eszter ; McBean, Douglas E. ; Olverman, Henry J. ; Bagdy, G. ; Kelly, Paul A T. / Persistent cerebrovascular effects of MDMA and acute responses to the drug. In: European Journal of Neuroscience. 2006 ; Vol. 24, No. 2. pp. 509-519.
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