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Mechan AO, O'Shea E, Elliott JM, Colado MI, Green AR. 
“A neurotoxic dose of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) to rats results in a long term defect in thermoregulation”. 
Psychopharmacology. 2001;155:413-418.

3,4-Methylenedioxymethamphetamine (MDMA; “ecstasy”) administration to rats produces damage to cerebral 5-HT nerve endings; however, the long-term functional consequences of this damage are poorly understood.
To confirm that MDMA administration produces a long-term effect on thermoregulation and investigate the mechanisms involved.

Male Dark Agouti rats were injected with a neurotoxic dose of MDMA (12.5 mg/kg IP). Five to 6 weeks later, they were exposed to high ambient temp (30°C) for 60 min followed by a return to normal temp (20°C), with rectal temperature being measured under both conditions. Further groups of MDMA-pretreated rats were challenged with 8-OH-DPAT and their temperature response measured.

MDMA administration produced acute hyperthermia. Rectal temperature had normalised 24 h later and was similar to saline-injected controls over the following 15 days. MDMA administration produced a 37% loss in hypothalamic 5-HT content 18 days later. When MDMA-pretreated rats were subjected to high ambient temperature 33 days post-treatment, they displayed both a faster rise in rectal temperature and sustained hyperthermia when returned to normal conditions. There was no difference in their hypothermic response to the 5-HT 1A agonist 8-OH-DPAT. Conclusions: A neurotoxic dose of MDMA resulted in impaired thermoregulation when rats were exposed to high ambient temperature. 5-HT 1A receptor mechanisms were unaltered. Impaired serotonergic function following MDMA presumably alters the neurotransmitter balance, thereby compromising thermoregulation. Heavy recreational users of MDMA may also have impaired thermo-regulation and thus be at greater risk of an acute adverse response to MDMA in a hot crowded dance environment.
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