PMID- 14985928
OWN - NLM
STAT- MEDLINE
DCOM- 20041122
LR  - 20181113
IS  - 0033-3158 (Print)
IS  - 0033-3158 (Linking)
VI  - 173
IP  - 3-4
DP  - 2004 May
TI  - Acute methylenedioxymethamphetamine administration: effects on local cerebral 
      blood flow and glucose utilisation in the Dark Agouti rat.
PG  - 287-95
AB  - 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.
FAU - Quate, Linda
AU  - Quate L
AD  - School of Health Sciences, Queen Margaret University College, Edinburgh, EH12 
      8TS, UK.
FAU - McBean, Douglas E
AU  - McBean DE
FAU - Ritchie, Isobel M
AU  - Ritchie IM
FAU - Olverman, Henry J
AU  - Olverman HJ
FAU - Kelly, Paul A T
AU  - Kelly PA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040220
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - IY9XDZ35W2 (Glucose)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Brain/blood supply/*drug effects/metabolism
MH  - Cerebrovascular Circulation/*drug effects
MH  - Glucose/*metabolism
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Rats
EDAT- 2004/02/27 05:00
MHDA- 2004/12/16 09:00
CRDT- 2004/02/27 05:00
PHST- 2003/10/01 00:00 [received]
PHST- 2003/12/17 00:00 [accepted]
PHST- 2004/02/27 05:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/02/27 05:00 [entrez]
AID - 10.1007/s00213-004-1784-z [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2004 May;173(3-4):287-95. doi: 
      10.1007/s00213-004-1784-z. Epub 2004 Feb 20.