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Persistent MDMA‐induced dopaminergic neurotoxicity in the striatum and substantia nigra of mice
Author(s) -
Granado Noelia,
O’Shea Esther,
Bove Jordi,
Vila Miquel,
Colado Mª Isabel,
Moratalla Rosario
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05705.x
Subject(s) - substantia nigra , dopaminergic , mdma , striatum , dopamine , tyrosine hydroxylase , dopamine transporter , neurotoxicity , medicine , endocrinology , glial fibrillary acidic protein , pharmacology , chemistry , neuroscience , biology , toxicity , immunohistochemistry
Acute administration of repeated doses of 3,4‐methylenedioxymethamphetamine (MDMA, ecstasy) dramatically reduces striatal dopamine (DA) content, tyrosine hydroxylase (TH), and DA transporter‐immunoreactivity in mice. In this study, we show for the first time the spatiotemporal pattern of dopaminergic damage and related molecular events produced by MDMA administration in mice. Our results include the novel finding that MDMA produces a significant decrease in the number of TH‐immunoreactive neurons in the substantia nigra (SN). This decrease appears 1 day after injection, remains stable for at least 30 days, and is accompanied by a dose‐dependent long‐lasting decrease in TH‐ and DA transporter‐immunoreactivity in the striatum, which peaked 1 day after treatment and persisted for at least 30 days, however, some recovery was evident from day 3 onwards, evidencing sprouting of TH fibers. No change is observed in the NAc indicating that MDMA causes selective destruction of DA‐containing neurons in the nigrostriatal pathway, sparing the mesolimbic pathway. The expression of Mac‐1 increased 1 day after MDMA treatment and glial fibrillary acidic protein increased 3 days post‐treatment in the striatum and SN but not in the NAc, in strict anatomical correlation with dopaminergic damage. These data provide the first evidence that MDMA causes persistent loss of dopaminergic cell bodies in the SN.