Alpha-lipoic Acid Prevents 3,4-methylenedioxy-methamphetamine (MDMA)-induced Neurotoxicity

Neuroreport. 1999 Nov 26;10(17):3675-80. doi: 10.1097/00001756-199911260-00039.

Abstract

A single administration of 3,4-methylenedioxymethamphetamine (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 alpha-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Binding Sites / drug effects
  • Carrier Proteins / metabolism
  • Fever / chemically induced
  • Frontal Lobe / cytology
  • Frontal Lobe / drug effects*
  • Frontal Lobe / metabolism
  • Glial Fibrillary Acidic Protein / analysis
  • Hippocampus / cytology
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Hypothermia / chemically induced
  • Male
  • Membrane Glycoproteins / metabolism
  • Membrane Transport Proteins*
  • N-Methyl-3,4-methylenedioxyamphetamine / antagonists & inhibitors
  • N-Methyl-3,4-methylenedioxyamphetamine / toxicity*
  • Neostriatum / cytology
  • Neostriatum / drug effects*
  • Neostriatum / metabolism
  • Nerve Tissue Proteins*
  • Neuroprotective Agents / pharmacology*
  • Paroxetine / metabolism
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / metabolism
  • Rats
  • Rats, Wistar
  • Serotonin / metabolism
  • Serotonin Plasma Membrane Transport Proteins
  • Thioctic Acid / pharmacology*

Substances

  • Antioxidants
  • Carrier Proteins
  • Glial Fibrillary Acidic Protein
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • Serotonin Plasma Membrane Transport Proteins
  • Slc6a4 protein, rat
  • Serotonin
  • Paroxetine
  • Thioctic Acid
  • N-Methyl-3,4-methylenedioxyamphetamine