PMID- 16836637
OWN - NLM
STAT- MEDLINE
DCOM- 20061003
LR  - 20131121
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 24
IP  - 2
DP  - 2006 Jul
TI  - Persistent cerebrovascular effects of MDMA and acute responses to the drug.
PG  - 509-19
AB  - 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 [(14)C]-iodoantipyrine and [(14)C]-2-deoxyglucose, respectively. 
      Serotonergic terminal depletion was assessed using radioligand binding with 
      [(3)H]-paroxetine and immunohistochemistry. Three weeks after MDMA pre-treatment 
      there were significant reductions in densities of 5-HT transporter 
      (SERT)-positive fibres (-46%) and [(3)H]-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.
FAU - Ferrington, Linda
AU  - Ferrington L
AD  - Division of Neuroscience, University of Edinburgh, 1 George Square, Edinburgh EH8 
      9JZ, UK. linda.ferrington@ed.ac.uk
FAU - Kirilly, Eszter
AU  - Kirilly E
FAU - McBean, Douglas E
AU  - McBean DE
FAU - Olverman, Henry J
AU  - Olverman HJ
FAU - Bagdy, Gyorgy
AU  - Bagdy G
FAU - Kelly, Paul A T
AU  - Kelly PA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060712
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Carbon Radioisotopes)
RN  - 0 (Serotonin Agents)
RN  - 333DO1RDJY (Serotonin)
RN  - 9G2MP84A8W (Deoxyglucose)
RN  - IY9XDZ35W2 (Glucose)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - T3CHA1B51H (Antipyrine)
RN  - V30V6H1QX4 (iodoantipyrine)
SB  - IM
MH  - Acute Disease
MH  - Animals
MH  - Antipyrine/analogs & derivatives/metabolism
MH  - Autonomic Pathways/drug effects/metabolism/physiopathology
MH  - Carbon Radioisotopes
MH  - Cerebral Arteries/*drug effects/innervation/physiopathology
MH  - Cerebral Cortex/blood supply/drug effects/physiopathology
MH  - Cerebrovascular Circulation/*drug effects/physiology
MH  - Cerebrovascular Disorders/*chemically induced/metabolism/physiopathology
MH  - Deoxyglucose/metabolism
MH  - Glucose/metabolism
MH  - Homeostasis/drug effects/physiology
MH  - Hyperemia/chemically induced/metabolism/physiopathology
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*adverse effects
MH  - Presynaptic Terminals/*drug effects/metabolism
MH  - Radioligand Assay
MH  - Rats
MH  - Serotonin/metabolism
MH  - Serotonin Agents/adverse effects
MH  - Stroke/chemically induced/metabolism/physiopathology
MH  - Synaptic Transmission/drug effects/physiology
MH  - Time
MH  - Vasoconstriction/drug effects/physiology
EDAT- 2006/07/14 09:00
MHDA- 2006/10/04 09:00
CRDT- 2006/07/14 09:00
PHST- 2006/07/14 09:00 [pubmed]
PHST- 2006/10/04 09:00 [medline]
PHST- 2006/07/14 09:00 [entrez]
AID - EJN4923 [pii]
AID - 10.1111/j.1460-9568.2006.04923.x [doi]
PST - ppublish
SO  - Eur J Neurosci. 2006 Jul;24(2):509-19. doi: 10.1111/j.1460-9568.2006.04923.x. 
      Epub 2006 Jul 12.