Cutaneous Vasoconstriction Contributes to Hyperthermia Induced by 3,4-Methylenedioxymethamphetamine (Ecstasy) in Conscious Rabbits

MDMA (Ecstasy) raises body temperature partly by constricting blood vessels near the skin's surface, which reduces the body's ability to release heat. In conscious rabbits, MDMA caused a dose-dependent increase in body temperature (from about 38.3 to 41.2 °C after 6 mg/kg) along with a sharp drop in ear pinna blood flow (from 29 to 5 cm/sec), indicating cutaneous vasoconstriction. Blocking sympathetic nerves on one side of the head reduced both the temperature rise and the vasoconstriction. This suggests that sympathetically mediated skin vessel narrowing is a key mechanism behind MDMA-induced hyperthermia, and reversing that constriction might help treat life-threatening overheating in humans.

Study at a glance

Abstract

3,4-Methylenedioxymethamphetamine (MDMA; "Ecstasy") increases body temperature. This process could be associated with increased cutaneous blood flow, as normally occurs with exercise-induced hyperthermia. Alternatively, an MDMA-induced fall in cutaneous blood flow could contribute to the hyperthermia by diminishing normal heat transfer from the body to the environment. We investigated these possibilities by administering MDMA (1.5-6 mg/kg, i.v.) to conscious freely moving rabbits, determining effects on body temperature, cutaneous blood flow (measured by a Doppler ultrasonic probe that was chronically implanted around the ear pinna artery), and other cardiovascular parameters. MDMA caused a dose-dependent increase in body temperature (from 38.3 +/- 0.3 to 41.2 +/- 0.4 degrees C after 6 mg/kg; p < 0.01; n = 5), preceded and accompanied by a dose-dependent cutaneous vasoconstriction (from 29 +/- 6 to 5 +/- 1 cm/sec after 6 mg/kg; p < 0.01; n = 5). MDMA (3 mg/kg) did not change blood flow to the mesenteric vascular bed. Prior unilateral cervical sympathectomy reduced the increase in body temperature elicited by MDMA (6 mg/kg) from 2.0 +/- 0.2 to 1.3 +/- 0.2 degrees C (p < 0.01; n = 5). On the denervated side, ear pinna blood flow after MDMA injection was 13 +/- 3 cm/sec, compared with 3 +/- 1 cm/sec on the sympathetically intact side (p < 0.05; n = 5). Thus, sympathetically mediated cutaneous vasoconstriction is one mechanism whereby MDMA causes hyperthermia. Reversal of cutaneous vasoconstriction by appropriate pharmacological means could be of therapeutic benefit in humans suffering from life-threatening hyperthermia induced by MDMA.