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Attenuation of the hyperthermia decreases the neurodegeneration. We have investigated the mechanisms involved in producing the neurotoxic loss of striatal dopamine.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>MDMA produced a dose\u2010dependent loss in striatal dopamine concentration 7 days later with 3 doses of 25\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup> (3\u2003h apart) producing a 70% loss.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Pretreatment 30 min before each MDMA dose with either of the N\u2010methyl\u2010D\u2010aspartate antagonists AR\u2010R15896AR (20, 5, 5\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>) or MK\u2010801 (0.5\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>\u00d73) failed to provide neuroprotection.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Pretreatment with clomethiazole (50\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>\u00d73) was similarly ineffective in protecting against MDMA\u2010induced dopamine loss.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The free radical trapping compound PBN (150\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>\u00d73) was neuroprotective, but it proved impossible to separate neuroprotection from a hypothermic effect on body temperature.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Pretreatment with the nitric oxide synthase (NOS) inhibitor 7\u2010NI (50\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>\u00d73) produced neuroprotection, but also significant hypothermia. Two other NOS inhibitors, S\u2010methyl\u2010L\u2010thiocitrulline (10\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>\u00d73) and AR\u2010R17477AR (5\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>\u00d73), provided significant neuroprotection and had little effect on MDMA\u2010induced hyperthermia.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>MDMA (20\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>) increased 2,3\u2010dihydroxybenzoic acid formation from salicylic acid perfused through a microdialysis tube implanted in the striatum, indicating increased free radical formation. This increase was prevented by AR\u2010R17477AR administration. Since AR\u2010R17477AR was also found to have no radical trapping activity this result suggests that MDMA\u2010induced neurotoxicity results from MDMA or dopamine metabolites producing radicals that combine with NO to form tissue\u2010damaging peroxynitrites.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2001) <jats:bold>134<\/jats:bold>, 1711\u20131723; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0704435\">10.1038\/sj.bjp.0704435<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0704435","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T21:39:21Z","timestamp":1106948361000},"page":"1711-1723","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":97,"title":["A study of the mechanisms involved in the neurotoxic action of 3,4\u2010methylenedioxymethamphetamine (MDMA, \u2018ecstasy\u2019) on dopamine neurones in mouse brain"],"prefix":"10.1111","volume":"134","author":[{"given":"M Isabel","family":"Colado","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Camarero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annis O","family":"Mechan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Sanchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blanca","family":"Esteban","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J Martin","family":"Elliott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A Richard","family":"Green","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"1104","article-title":"Methamphetamine\u2010induced hyperthermia and dopaminergic neurotoxicity in mice: pharmacological profile of protective and nonprotective agents","volume":"275","author":"ALBERS D.S.","year":"1995","journal-title":"J. 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