Document Detail


Acute methylenedioxymethamphetamine administration: effects on local cerebral blood flow and glucose utilisation in the Dark Agouti rat.
MedLine Citation:
PMID:  14985928     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Linda Quate; Douglas E McBean; Isobel M Ritchie; Henry J Olverman; Paul A T Kelly
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-02-20
Journal Detail:
Title:  Psychopharmacology     Volume:  173     ISSN:  0033-3158     ISO Abbreviation:  Psychopharmacology (Berl.)     Publication Date:  2004 May 
Date Detail:
Created Date:  2004-05-12     Completed Date:  2004-11-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7608025     Medline TA:  Psychopharmacology (Berl)     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  287-95     Citation Subset:  IM    
Affiliation:
School of Health Sciences, Queen Margaret University College, Edinburgh, EH12 8TS, UK.
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain / blood supply,  drug effects*,  metabolism
Cerebrovascular Circulation / drug effects*
Glucose / metabolism*
Male
N-Methyl-3,4-methylenedioxyamphetamine / pharmacology*
Rats
Chemical
Reg. No./Substance:
42542-10-9/N-Methyl-3,4-methylenedioxyamphetamine; 50-99-7/Glucose

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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