Persistent MDMA‐induced dopaminergic neurotoxicity in the striatum and substantia nigra of mice
Noelia Granado, Esther O’shea, Jordi Bové, Miquel Vila, María Isabel Colado, Rosario Moratalla
Journal of Neurochemistry September 24, 2008 DOI: 10.1111/j.1471-4159.2008.05705.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Duration | 1 day to at least 30 days post-injection |
| Topics | MDMA |
| Keywords | Substantia nigra Dopaminergic Striatum Neurotoxicity Midbrain Pharmacology |
| Citations | 112 |
| Key findings | MDMA causes a persistent loss of dopaminergic cell bodies in the substantia nigra and selective damage to the nigrostriatal pathway in mice. |
Abstract
Abstract 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.