title: Cutaneous vasoconstriction contributes to hyperthermia induced by 3,4-methylenedioxymethamphetamine (ecstasy) in conscious rabbits.
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.
authors.affiliation: Departments of Medicine and Physiology, Centre for Neuroscience, Flinders University, Bedford Park 5042, South Australia, Australia.
authors.forename: N P
authors.initials: NP
authors.lastname: Pedersen
authors.forename: W W
authors.initials: WW
authors.lastname: Blessing
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D003080:Cold Temperature; D004305:Dose-Response Relationship, Drug; D005334:Fever / Q000139:chemically induced*; D006339:Heart Rate / Q000187:drug effects; D006358:Hot Temperature; D016014:Linear Models; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000502:physiology; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D011817:Rabbits; D015203:Reproducibility of Results; D012867:Skin / Q000098:blood supply / Q000187:drug effects*; D012879:Skin Physiological Phenomena / Q000187:drug effects*; D013562:Sympathectomy; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D018817:N-Methyl-3,4-methylenedioxyamphetamine