α-Lipoic acid prevents 3,4-methylenedioxy-methamphetamine (MDMA)-induced neurotoxicity

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.

Study at a glance

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.