Neuroreport
November 1, 1999
Norberto Aguirre, Meritxell Barrionuevo, Marı́a J. Ramı́rez et al.
89 citations
A single dose of MDMA (20 mg/kg) given to rats caused significant hyperthermia and reduced serotonin content and serotonin transporter density by 40–60% in the frontal cortex, striatum, and hippocampus one week later. MDMA also increased glial fibrillary acidic protein (GFAP) immunoreactivity in the hippocampus. Repeated administration of the metabolic antioxidant α-lipoic acid before MDMA did not prevent the acute hyperthermia but fully prevented the serotonergic deficits and glial changes. These results support the hypothesis that free radical formation is responsible for MDMA-induced neurotoxicity.
European journal of pharmacology
May 21, 2007
Beatriz Goñi-allo, Elena Puerta, Isabel Hervias et al.
13 citations
Amiloride, a drug that blocks sodium/calcium and sodium/hydrogen exchange, worsens long-term serotonin loss caused by MDMA in rats. Unlike with methamphetamine, amiloride also increases MDMA-induced hyperthermia. The antidepressant fluoxetine fully protects against serotonin depletion without affecting hyperthermia, while calcium channel blockers do not. The effect appears mediated by sodium/hydrogen exchange blockade, as dimethylamiloride produces similar results. When rats are kept at 15°C, hyperthermia does not develop and serotonin levels remain normal after seven days. These findings suggest that amiloride's enhancement of serotonin loss depends on its ability to amplify MDMA-induced hyperthermia, and that blocking sodium/hydrogen exchange may combine with hyperthermia to make serotonin nerve endings more vulnerable.
Pharmaceuticals
July 5, 2011
Elena Puerta, Norberto Aguirre
6 citations
MDMA (ecstasy) causes long-lasting reductions in markers of serotonin neurons in animal brains, including decreased tryptophan hydroxylase activity, lower serotonin and its metabolite 5-HIAA, and reduced binding to serotonin transporters. Similar reductions in 5-HIAA and serotonin transporter density have been observed in human ecstasy users, suggesting loss of serotonergic fibers. However, some recent studies failed to show loss of the serotonin transporter protein or reactive astrogliosis after MDMA exposure, and MDMA also down-regulates serotonin transporter gene expression. These findings have led to debate: decreased protein levels do not necessarily indicate neurodegeneration, but neuromodulatory mechanisms do not rule out serotonin terminal degeneration.