α-Lipoic acid prevents 3,4-methylenedioxy-methamphetamine (MDMA)-induced neurotoxicity
Neuroreport – November 01, 1999
Source: OpenAlex
Summary
A single dose of MDMA (20 mg/kg) caused significant hyperthermia in rats and led to a 40-60% reduction in serotonin levels and transporter density in key brain regions like the frontal cortex, striatum, and hippocampus after one week. Additionally, MDMA increased glial fibrillary acidic protein (GFAP) in the hippocampus. Interestingly, administering α-lipoic acid (100 mg/kg) before MDMA did not prevent hyperthermia but completely countered serotonin deficits and glial changes, suggesting that free radical formation drives MDMA's neurotoxic effects.
Abstract
A single administration of 3,4-methylenedioxymetham-phetamine (MDMA, 20 mg/kg, i.p.), induced significant hyperthermia in rats and reduced 5-hydroxytryptamine (5-HT) content and [3H]paroxetine-labeled 5-HT transporter density in the frontal cortex, striatum and hippocampus by 40–60% 1 week later. MDMA treatment also increased glial fibrillary acidic protein (GFAP) immunoreactivity in the hippocampus. Repeated administration of the metabolic antioxidant α-lipoic acid (100 mg/kg, i.p., b.i.d. for 2 consecutive days) 30 min prior to MDMA did not prevent the acute hyperthermia induced by the drug; however, it fully prevented the serotonergic deficits and the changes in the glial response induced by MDMA. These results further support the hypothesis that free radical formation is responsible for MDMA-induced neurotoxicity.