A neurotoxic dose of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) to rats results in a long term defect in thermoregulation

Rationale: 3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") administrati on to rats produces damage to cerebral 5-HT nerve endings; however, the lon g-term functional consequences of this damage are poorly understood. Object ive: To confirm that MDMA administration produces a long-term effect on the rmoregulation and investigate the mechanisms involved. Methods: Male Dark A gouti rats were injected with a neurotoxic dose of MDMA (12.5 mg/kg IF). Fi ve to 6 weeks later, they were exposed to high ambient temp (30 degreesC) f or 60 min followed by a return to normal temp (20 degreesC), with rectal te mperature being measured under both conditions. Further groups of MDMA-pret reated rats were challenged with 8-OH-DPAT and their temperature response m easured. Results: MDMA administration produced acute hyperthermia. Rectal t emperature had normalised 24 h later and was similar to saline-injected con trols over the following 15 days. MDMA administration produced a 37% loss i n hypothalamic 5-HT content 18 days later. When MDMA-pretreated rats were s ubjected to high ambient temperature 33 days posttreatment, they displayed both a faster rise in rectal temperature and sustained hyperthermia when re turned to normal conditions. There was no difference in their hypothermic r esponse to the 5-HT,, agonist 8-OH-DPAT, Conclusions: A neurotoxic dose of MDMA resulted in impaired thermoregulation when rats MDMA presumably alters the neurotransmitter balance, thereby compromising thermoregulation. Heavy recreational users of MDMA may also have impaired thermoregulation and thu s be at greater risk of an acute adverse response to MDMA in a hot crowded dance environment.