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The Journal of Neuroscience, November 1, 2001, 21(21):8648-8654

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

N. P. Pedersen and W. W. Blessing

Departments of Medicine and Physiology, Centre for Neuroscience, Flinders University, Bedford Park 5042, South Australia, Australia

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°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°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.

Key words: MDMA; ecstasy; temperature regulation; skin blood flow; heat loss; serotonin; 5-HT; hyperthermia

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Copyright © 2001 Society for Neuroscience  0270-6474/01/21218648-07$05.00/0

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