3,4-Methylenedioxymethamphetamine increases interleukin-1beta levels and activates microglia in rat brain: studies on the relationship with acute hyperthermia and 5-HT depletion

J Neurochem. 2004 Jun;89(6):1445-53. doi: 10.1111/j.1471-4159.2004.02443.x.


3,4-Methylenedioxymethamphetamine (MDMA) administration to rats produces acute hyperthermia and 5-HT release. Interleukin-1beta (IL-1beta) is a pro-inflammatory pyrogen produced by activated microglia in the brain. We examined the effect of a neurotoxic dose of MDMA on IL-1beta concentration and glial activation and their relationship with acute hyperthermia and 5-HT depletion. MDMA, given to rats housed at 22 degrees C, increased IL-1beta levels in hypothalamus and cortex from 1 to 6 h and [(3)H]-(1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)3-isoquinolinecarboxamide) binding between 3 and 48 h. Increased immunoreactivity to OX-42 was also detected. Rats became hyperthermic immediately after MDMA and up to at least 12 h later. The IL-1 receptor antagonist did not modify MDMA-induced hyperthermia indicating that IL-1beta release is a consequence, not the cause, of the rise in body temperature. When MDMA was given to rats housed at 4 degrees C, hyperthermia was abolished and the IL-1beta increase significantly reduced. The MDMA-induced acute 5-HT depletion was prevented by fluoxetine coadministration but the IL-1beta increase and hyperthermia were unaffected. Therefore, the rise in IL-1beta is not related to the acute 5-HT release but is linked to the hyperthermia. Contrary to IL-1beta levels, microglial activation is not significantly modified when hyperthermia is prevented, suggesting that it might be a process not dependent on the hyperthermic response induced by MDMA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Binding, Competitive / drug effects
  • Binding, Competitive / physiology
  • Body Temperature / drug effects
  • Brain / drug effects*
  • Brain / metabolism
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Fever / chemically induced*
  • Fever / drug therapy
  • Fever / metabolism
  • Fluoxetine / pharmacology
  • Glial Fibrillary Acidic Protein / metabolism
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / metabolism*
  • Isoquinolines / pharmacokinetics
  • Male
  • Microglia / drug effects*
  • Microglia / metabolism
  • N-Methyl-3,4-methylenedioxyamphetamine / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Serotonin / deficiency
  • Serotonin / metabolism*
  • Serotonin Agents / pharmacology
  • Sialoglycoproteins / pharmacology
  • Temperature


  • Glial Fibrillary Acidic Protein
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Isoquinolines
  • Serotonin Agents
  • Serotonin Uptake Inhibitors
  • Sialoglycoproteins
  • Fluoxetine
  • Serotonin
  • N-Methyl-3,4-methylenedioxyamphetamine
  • PK 11195