Effects of 3,4-methylenedioxymethamphetamine on autonomic thermoregulatory responses of the rat

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3,4-Methylenedioxymethamphetamine (MDMA), a substituted amphetamine analogue which stimulates serotonin release in the CNS, has been shown to induce near lethal elevations in core temperature in the rat. To characterize the effects of MDMA on temperature regulation, we measured metabolic rate (MR), evaporative water loss (EWL), motor activity (MA), and colonic temperature (T c) in male, Long-Evans rats at 60 min following 30 mg/kg (SC) MDMA or saline at ambient temperatures (T a) of 10, 20, and 30°C. MDMA caused an elevation in MR at T a's of 20 and 30°C but had no effect at 10°C. At a T a of 30°C, MR of the MDMA group was double that of the saline group. EWL was elevated by MDMA, an effect which was potentiated with increasing T a. MDMA also elicited an increase in MA at all three T a's. MDMA led to a 3.2°C increase in T c at 30°C, no change in T c at 20°C, and a 2.0°C decrease in T c at 10°C. A second study found that treatment with 20 mg/kg MDMA failed to elicit an increase in blood flow to the tail in spite of a hyperthermic core temperature of 41.4°C. Preliminary studies using radiotelemetry methodology suggested that MDMA lethality is preceded by precipitous elevations in heart rate and core temperature. The data suggest that, at relatively warm T a's, MDMA-induced stimulation of serotonergic pathway causes an elevation in MR and peripheral vasoconstriction, thus producing life-threatening elevations in T c. The increase in EWL following MDMA partially attenuates the hyperthermia at warm T a's, but leads to hypothermia in the rat maintained at a cold T a of 10°C.