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Keywords:

  • 3,4-methylenedioxymethamphetamine;
  • ecstasy;
  • hyperthermia;
  • dopamine;
  • 5-hydroxytryptamine;
  • 5-HT antagonists;
  • dopamine antagonists;
  • GBR 12909;
  • fluoxetine
  • The pharmacology of the acute hyperthermia that follows 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) administration to rats has been investigated.

  • MDMA (12.5 mg kg−1 i.p.) produced acute hyperthermia (measured rectally). The tail skin temperature did not increase, suggesting that MDMA may impair heat dissipation.

  • Pretreatment with the 5-HT1/2 antagonist methysergide (10 mg kg−1), the 5-HT2A antagonist MDL 100,907 (0.1 mg kg−1) or the 5-HT2C antagonist SB 242084 (3 mg kg−1) failed to alter the hyperthermia. The 5-HT2 antagonist ritanserin (1 mg kg−1) was without effect, but MDL 11,939 (5 mg kg−1) blocked the hyperthermia, possibly because of activity at non-serotonergic receptors.

  • The 5-HT uptake inhibitor zimeldine (10 mg kg−1) had no effect on MDMA-induced hyperthermia. The uptake inhibitor fluoxetine (10 mg kg−1) markedly attenuated the MDMA-induced increase in hippocampal extracellular 5-HT, also without altering hyperthermia.

  • The dopamine D2 antagonist remoxipride (10 mg kg−1) did not alter MDMA-induced hyperthermia, but the D1 antagonist SCH 23390 (0.3 – 2.0 mg kg−1) dose-dependently antagonized it.

  • The dopamine uptake inhibitor GBR 12909 (10 mg kg−1) did not alter the hyperthermic response and microdialysis demonstrated that it did not inhibit MDMA-induced striatal dopamine release.

  • These results demonstrate that in vivo MDMA-induced 5-HT release is inhibited by 5-HT uptake inhibitors, but MDMA-induced dopamine release may not be altered by a dopamine uptake inhibitor.

  • It is suggested that MDMA-induced hyperthermia results not from MDMA-induced 5-HT release, but rather from the increased release of dopamine that acts at D1 receptors. This has implications for the clinical treatment of MDMA-induced hyperthermia.

British Journal of Pharmacology (2002) 135, 170–180; doi:10.1038/sj.bjp.0704442