A neurotoxic dose of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) to rats results in a long-term defect in thermoregulation.
BACKGROUND
3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") administration to rats produces damage to cerebral 5-HT nerve endings; however, the long-term functional consequences of this damage are poorly understood.


OBJECTIVE
To confirm that MDMA administration produces a long-term effect on thermoregulation and investigate the mechanisms involved.


METHODS
Male Dark Agouti rats were injected with a neurotoxic dose of MDMA (12.5 mg/kg i.p.). Five to 6 weeks later, they were exposed to high ambient temp (30 degrees C) for 60 min followed by a return to normal temp (20 degrees C), with rectal temperature being measured under both conditions. Further groups of MDMA-pretreated rats were challenged with 8-OH-DPAT and their temperature response measured.


RESULTS
MDMA administration produced acute hyperthermia. Rectal temperature had normalised 24 h later and was similar to saline-injected controls over the following 15 days. MDMA administration produced a 37% loss in hypothalamic 5-HT content 18 days later. When MDMA-pretreated rats were subjected to high ambient temperature 33 days posttreatment, they displayed both a faster rise in rectal temperature and sustained hyperthermia when returned to normal conditions. There was no difference in their hypothermic response to the 5-HT1A agonist 8-OH-DPAT.


CONCLUSIONS
A neurotoxic dose of MDMA resulted in impaired thermoregulation when rats were exposed to high ambient temperature. 5-HT1A receptor mechanisms were unaltered. Impaired serotonergic function following MDMA presumably alters the neurotransmitter balance, thereby compromising thermoregulation. Heavy recreational users of MDMA may also have impaired thermoregulation and thus be at greater risk of an acute adverse response to MDMA in a hot crowded dance environment.
Mechan
A O
AO
Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, De Montfort University, The Gateway, Leicester LE1 9BH, UK.
O'Shea
E
E
Elliott
J M
JM
Colado
M I
MI
Green
A R
AR
D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001833:Body Temperature Regulation / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects; D006213:Hallucinogens / Q000633:toxicity*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D020258:Neurotoxicity Syndromes / Q000503:physiopathology*; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D000662:Amphetamines; D006213:Hallucinogens; D010879:Piperazines; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D018817:N-Methyl-3,4-methylenedioxyamphetamine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; C015068:1-(3-chlorophenyl)piperazine