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

Abstract.

Rationale: 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. Objective: To confirm that MDMA administration produces a long-term effect on thermoregulation and investigate the mechanisms involved. Methods: 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. Results: 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 thermoregulation and thus be at greater risk of an acute adverse response to MDMA in a hot crowded dance environment.