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3,4-Methylenedioxymethamphetamine (MDMA, ‘ecstasy’) administration to rats produces hyperthermia if they are housed in normal or warm ambient room temperature (Ta) conditions (≥20°C), but hypothermia when in cool conditions (Ta≤17°C). We have now investigated some of the mechanisms involved.MDMA (5 mg kg−1 i.p.) produced a rapid decrease in rectal temperature in rats at Ta 15°C. This response was blocked by pretreatment with the dopamine D2 receptor antagonist remoxipride (10 mg kg−1 i.p.), but unaltered by pretreatment with the D1 antagonist SCH23390 (1.1 mg kg−1 i.p.).MDMA (5 mg kg−1) did not alter the tail temperature of rats at Ta 15°C, but decreased the tail temperature of rats at Ta 30°C.A neurotoxic dose of MDMA (three doses of 5 mg kg−1 given 3 h apart) decreased cortical and hippocampal 5-HT content by approximately 30% 7 days later. This lesion did not influence the rise in tail temperature when rats were moved from Ta 20°C to 30°C compared to nonlesioned controls, but did result in a lower tail temperature than that of controls when they were returned to Ta 24°C.Acute administration of MDMA (5 mg kg−1) to MDMA-lesioned rats produced a sustained decrease in tail temperature in rats housed at Ta 30°C compared to nonlesioned controls.These data suggest that the thermoregulatory problems previously observed in MDMA-lesioned rats housed at Ta 30°C result, partially, from their inability to lose heat by vasodilation of the tail, a major heat-loss organ in this species.