The pharmacology of the acute hyperthermic response that follows administration of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') to rats

1 The pharmacology of the acute hyperthermia that follows 3.4-methylenedioxymethamphetamine (MDMA. 'ecstasy') administration to rats has been investigated. 2 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. 3 Pretreatment with the 5-HT1 2 antagonist imethysergide (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-serotoriergic receptors. 4 The 5-HT uptake inhibitor zimeldine (10 mg kg (1)) had no effect oil 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. 5 The dopamine D-2 antagonist remoxipride (10 mg kg(-1)) did not alter MDMA-induced hyperthermia, but the D-1 antagonist SCH 23390 (0.3-2.0 mg kg(-1)) dose-dependently antagonized it. 6 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. 7 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. 8 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 D, receptors. This has implications for the clinical treatment of MDMA-induced hyperthermia.