Cutaneous vasoconstriction contributes to hyperthermia induced by 3,4-methylenedioxymethamphetamine (Ecstasy) in conscious rabbits

3,4-Methylenedioxymethamphetamine (MDMA; "Ecstasy") increases body temperat ure. This process could be associated with increased cutaneous blood flow, as normally occurs with exercise-induced hyperthermia. Alternatively, an MD MA-induced fall in cutaneous blood flow could contribute to the hyperthermi a 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 chr onically implanted around the ear pinna artery), and other cardiovascular p arameters. MDMA caused a dose-dependent increase in body temperature (from 38.3 +/- 0.3 to 41.2 +/- 0.4 degreesC after 6 mg/kg; p < 0.01; n = 5), prec eded and accompanied by a dose-dependent cutaneous vasoconstriction (from 2 9 +/- 6 to 5 +/- 1 cm/sec after 6 mg/kg; p < 0.01; n = 5). MDMA (3 mg/kg) d id not change blood flow to the mesenteric vascular bed. Prior unilateral c ervical sympathectomy reduced the increase in body temperature elicited by MDMA (6 mg/kg) from 2.0 +/- 0.2 to 1.3 +/- 0.2 degreesC (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 vasoconstrict ion is one mechanism whereby MDMA causes hyperthermia. Reversal of cutaneou s vasoconstriction by appropriate pharmacological means could be of therape utic benefit in humans suffering from life-threatening hyperthermia induced by MDMA.