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In the longer term the same single dose results in depletion of 5\u2010hydroxytrptamine (5\u2010HT) 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\u2010treated with 15\u2003mg\/kg i.p. MDMA or saline. Three weeks later, rats from each pre\u2010treatment group were treated with an acute dose of MDMA (15\u2003mg\/kg i.p.) or saline. Quantitative autoradiographic imaging was used to measure LCBF or LCMRglu with [<jats:sup>14<\/jats:sup>C]\u2010iodoantipyrine and [<jats:sup>14<\/jats:sup>C]\u20102\u2010deoxyglucose, respectively. Serotonergic terminal depletion was assessed using radioligand binding with [<jats:sup>3<\/jats:sup>H]\u2010paroxetine and immunohistochemistry. Three weeks after MDMA pre\u2010treatment there were significant reductions in densities of 5\u2010HT transporter (SERT)\u2010positive fibres (\u221246%) and [<jats:sup>3<\/jats:sup>H]\u2010paroxetine binding (\u221247%). In animals pre\u2010treated 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\u2010treatment groups, acute MDMA produced significant increases in LCMRglu, while LCBF was significantly decreased. In 50% of MDMA\u2010pre\u2010treated rats, random areas of focal hyperaemia indicated a loss of autoregulatory capacity in response to MDMA\u2010induced 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\u2010HT terminals. However, there may be a sub\u2010population, or individual circumstances, in which this dysfunction develops into a condition that might predispose to stroke.<\/jats:p>","DOI":"10.1111\/j.1460-9568.2006.04923.x","type":"journal-article","created":{"date-parts":[[2006,7,12]],"date-time":"2006-07-12T13:17:09Z","timestamp":1152710229000},"page":"509-519","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Persistent cerebrovascular effects of MDMA and acute responses to the drug"],"prefix":"10.1111","volume":"24","author":[{"given":"Linda","family":"Ferrington","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eszter","family":"Kirilly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas E.","family":"McBean","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry J.","family":"Olverman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gy\u00f6rgy","family":"Bagdy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul A. 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