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

https://doi.org/10.1016/0091-3057(91)90288-DGet rights and content

Abstract

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 (Tc) in male, Long-Evans rats at 60 min following 30 mg/kg (SC) MDMA or saline at ambient temperatures (Ta) of 10, 20, and 30°C. MDMA caused an elevation in MR at Ta's of 20 and 30°C but had no effect at 10°C. At a Ta 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 Ta. MDMA also elicited an increase in MA at all three Ta's. MDMA led to a 3.2°C increase in Tc at 30°C, no change in Tc at 20°C, and a 2.0°C decrease in Tc 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 Ta's, MDMA-induced stimulation of serotonergic pathway causes an elevation in MR and peripheral vasoconstriction, thus producing life-threatening elevations in Tc. The increase in EWL following MDMA partially attenuates the hyperthermia at warm Ta's, but leads to hypothermia in the rat maintained at a cold Ta of 10°C.

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    This mortality rate is notable as the commonly accepted LD50 for intraperitoneally injected MDMA in the rat is 49 mg/kg (Hardman et al., 1973). The results gathered by our improved probe support previous data that high ambient temperatures exacerbate the MDMA-induced hyperthermic response (Gordon et al., 1991; Malberg and Seiden, 1998; Seiden and Sabol, 1996). It is well known that the brain is the most temperature sensitive organ in the body and even small deviations in temperature can have profound negative impacts within the brain (Schiff and Somjen, 1985), thus an effective means of localized thermometry is required to better assess and understand these impacts.

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This paper has been reviewed by the Health Effects Research Laboratory, U.S. Environemtal Protection Agency, and approved for publication. Mention of trade names or commmercial products does not constitute endorsement or recommendation for use.

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Work supported in part by National Institute of Drug Abuse IAG RA89-4.

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