SMALL CHANGES IN AMBIENT-TEMPERATURE CAUSE LARGE CHANGES IN 3,4-METHYLENEDIOXYMETHAMPHETAMINE (MDMA)-INDUCED SEROTONIN NEUROTOXICITY AND CORE BODY-TEMPERATURE IN THE RAT

The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA) is a drug of abuse and has been shown to be neurotoxic to 5-HT terminals in many species. MDMA-engendered neurotoxicity has been shown to be a ffected by both ambient temperature and core body temperature. We now report that small (2 degrees C) changes in ambient temperature produce changes in core temperature in MDMA-treated rats, but the same change s in ambient temperature do not affect core temperature of saline-trea ted animals. Furthermore, increases in core temperature of MDMA-treate d animals increase neurotoxicity. Rats were given MDMA (20 or 40 mg/kg ) or saline and placed in an ambient temperature of 20, 22, 24, 26, 28 , or 30 degrees C using a novel temperature measurement apparatus that controls ambient temperature +/-0.5 degrees C. Two weeks after MDMA t reatment, the rats were killed, and regional 5-HT and 5-hydroxyindole acetic acid levels were analyzed as a measure of neurotoxicity. Rats t reated with MDMA at 20 and 22 degrees C showed a hypothermic core temp erature response. Treatment with MDMA at 28 and 30 degrees C produced a hyperthermic response. At ambient temperatures of 20-24 degrees C, n eurotoxicity was not observed in the frontal cortex, somatosensory cor tex, hippocampus, or striatum. At ambient temperatures of 26-30 degree s C, neurotoxicity was seen and correlated with core temperature in al l regions examined. These data indicate that ambient temperature has a significant affect on MDMA neurotoxicity, core temperature, and therm oregulation in rats. This finding has implications on both the tempera ture dependence of the mechanism of MDMA neurotoxicity and human use b ecause fatal hyperthermia is associated with MDMA use in humans.