Caffeine enhances astroglia and microglia reactivity induced by 3,4-methylenedioxymethamphetamine ('ecstasy') in mouse brain

Neurotox Res. 2010 May;17(4):435-9. doi: 10.1007/s12640-009-9125-y. Epub 2009 Oct 31.


Several reports suggest that 3,4-methylenedioxymethamphetamine (MDMA) induces neurotoxic effects and gliosis. Since recreational use of MDMA is often associated with caffeinated beverages, we investigated whether caffeine interferes with MDMA-induced astroglia and microglia activation, thus facilitating its neurotoxicity. MDMA (4 x 20 mg/kg) was acutely administered to mice alone or in combination with caffeine (10 mg/kg). CD11b and GFAP immunoreactivity were evaluated as markers of microglia and astroglia activation in the substantia nigra pars-compacta (SNc) and striatum. MDMA was associated with significantly higher CD11b and GFAP immunoreactivity in striatum, whereas only CD11b was significantly higher than vehicle in SNc. Caffeine potentiated the increase in CD11b and GFAP in the striatum but not in the SNc of MDMA-treated mice. The abuse of MDMA is a growing worldwide problem; the results of this study suggest that combination of MDMA plus caffeine by increasing glial activation might have harmful health consequences.

MeSH terms

  • Animals
  • Astrocytes / drug effects*
  • Brain / cytology*
  • Brain / drug effects*
  • CD11b Antigen / metabolism
  • Caffeine / pharmacology*
  • Drug Interactions
  • Gene Expression Regulation / drug effects
  • Glial Fibrillary Acidic Protein / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microglia / drug effects*
  • N-Methyl-3,4-methylenedioxyamphetamine / toxicity*
  • Phosphodiesterase Inhibitors / pharmacology*


  • CD11b Antigen
  • Glial Fibrillary Acidic Protein
  • Phosphodiesterase Inhibitors
  • Caffeine
  • N-Methyl-3,4-methylenedioxyamphetamine