Persistent loss of thermoregulation in the rat induced by 3,4-methylenedioxymethamphetamine (MDMA or "Ecstasy") but not by fenfluramine.
Using radio-biotelemetry, the timecourse of recovery and sensitivity to ambient temperature (Ta) of the thermogenic response of methylenedioxymethamphetamine (MDMA or "Ecstasy") was examined. Ambient temperatures of 17 and 22 degrees C produced very different response profiles, with the lower temperature producing a hypothermic response to 10 and 15 mg/kg doses of MDMA, and the higher temperature producing a profound hyperthermia to the same doses. Although the peak responses to the drug had subsided within 5 h of administration, residual effects, in the form of an elevation of body temperature during the "low" phase of the diurnal cycle, were present for a further 48 h. Long-lasting disruption of the thermoregulatory system following a short series of MDMA administrations (10 mg/kg once per day for 4 days) was shown by exposing the rats in the undrugged state to a thermoregulatory challenge, consisting of 60-min exposure to a Ta of 30 degrees C, at 1 week before, and at 4 weeks and 14 weeks after the drug administration. MDMA-treated rats showed a prolonged hyperthermic response to the challenge at both post-drug intervals compared with fenfluramine-treated rats and saline-treated controls. Thus, the results indicate both that MDMA's thermogenic effects are more sensitive to Ta than previously demonstrated, and that the serotonergic neurotoxicity of the drug may produce long-lasting changes in thermoregulatory mechanisms.
Dafters
R I
RI
Psychology Department, Glasgow University, UK.
Lynch
E
E
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D015259:Dopamine Agents / Q000494:pharmacology; D005260:Female; D005277:Fenfluramine / Q000494:pharmacology*; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018490:Serotonin Agents / Q000494:pharmacology*
D015259:Dopamine Agents; D018490:Serotonin Agents; D005277:Fenfluramine; D000661:Amphetamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine