3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) produces edema due to BBB disruption induced by MMP-9 activation in rat hippocampus.
Mercedes Pérez-Hernández, María Encarnación Fernández-Valle, Ana Rubio-Araiz, Rebeca Vidal, María Dolores Gutiérrez‐lópez, Esther O'Shea, María Isabel Colado
Neuropharmacology March 16, 2017 DOI: 10.1016/j.neuropharm.2017.03.019 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled experimental animal study Peer reviewed |
|---|---|
| Population | Adult male Dark Agouti rats |
| Interventions | MDMA SB-3CT |
| Dose | MDMA 12.5 mg/kg, i.p.; SB-3CT 25 mg/kg, i.p. |
| Measures | Evans Blue dye extravasation |
| Topics | MDMA |
| Keywords | Blood-brain barrier Animals Rats Brain edema Disease models, animal N-methyl-3,4-methylenedioxyamphetamine Sulfones Heterocyclic compounds, 1-ring Plasminogen Hallucinogens Enzyme inhibitors Magnetic resonance imaging Gene expression regulation Permeability Time factors Male Aquaporin 4 Matrix metalloproteinase 9 Claudin-5 Mmp-9 Aqp4 Sb-3ct pubchem cid |
| Key findings | The authors conclude that a single 12.5 mg/kg dose of MDMA produces short-duration brain edema in rats through blood-brain barrier disruption mediated by MMP-9 activation, associated with altered AQP4 expression and reduced claudin-5 expression. The MMP-9 inhibitor SB-3CT prevented these changes, and MDMA also transiently increased tPA activity and expression. |
Abstract
The recreational drug of abuse, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) disrupts blood-brain barrier (BBB) integrity in rats through an early P2X7 receptor-mediated event which induces MMP-9 activity. Increased BBB permeability often causes plasma proteins and water to access cerebral tissue leading to vasogenic edema formation. The current study was performed to examine the effect of a single neurotoxic dose of MDMA (12.5 mg/kg, i.p.) on in vivo edema development associated with changes in the expression of the perivascular astrocytic water channel, AQP4, as well as in the expression of the tight-junction (TJ) protein, claudin-5 and Evans Blue dye extravasation in the hippocampus of adult male Dark Agouti rats. We also evaluated the ability of the MMP-9 inhibitor, SB-3CT (25 mg/kg, i.p.), to prevent these changes in order to validate the involvement of MMP-9 activation in MDMA-induced BBB disruption. The results show that MDMA produces edema of short duration temporally associated with changes in AQP4 expression and a reduction in claudin-5 expression, changes which are prevented by SB-3CT. In addition, MDMA induces a short-term increase in both tPA activity and expression, a serine-protease which is involved in BBB disruption and upregulation of MMP-9 expression. In conclusion, this study provides evidence enough to conclude that MDMA induces edema of short duration due to BBB disruption mediated by MMP-9 activation.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
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