Effect of ambient temperature and a prior neurotoxic dose of 3,4-methylenedioxymethamphetamine (MDMA) on the hyperthermic response of rats to a single or repeated ('binge' ingestion) low dose of MDMA.
BACKGROUND
3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) administration to rats produces acute hyperthermia and long-term neurotoxic damage to 5-hydroxytryptamine (serotonin, 5-HT) neurones.


OBJECTIVE
We wished to examine MDMA-induced hyperthermia in rats housed at normal (19 degrees C) and high (30 degrees C) room temperatures and investigate the effect of a prior neurotoxic lesion.


METHODS
Rectal temperature was measured after administration of single or repeated doses of MDMA to rats housed at 19 degrees C and 30 degrees C.


RESULTS
MDMA (5 mg/kg i.p.) produced a sustained hyperthermic response in rats housed at 30 degrees C, but not in rats housed at 19 degrees C. A prior (5 weeks earlier) neurotoxic dose of MDMA (12.5 mg/kg i.p.) resulted in MDMA (5 mg/kg) producing a greater hyperthermic response in rats housed at 30 degrees C than in non-pre-treated animals. Repeated MDMA administration (binge dosing; 2, 4 or 6 mg/kg x3) produced dose-dependent hyperthermia in rats housed at 19 degrees C, with MDMA (2 mg/kg x3) having little effect. However, this dose produced significant hyperthermia (> or =2 degrees C above control values)in rats housed at 30 degrees C following the third dose. A prior neurotoxic dose of MDMA resulted in MDMA (2 mg/kg x3) producing marked hyperthermia (>1 degrees C) after the first dose and severe hyperthermia (> or =2 degrees C) after the third dose.


CONCLUSIONS
MDMA administration to rats housed at 30 degrees C produces a more severe hyperthermic response than that seen in rats housed at 19 degrees C. A prior neurotoxic dose enhances the response further in animals housed at 30 degrees C. Binge dosing produces a higher final peak response than a similar non-divided dose. This effect is more marked in animals housed at high room temperature. These data may have implications for recreational users of MDMA in hot environments, particularly those who may have damaged serotoninergic neurones because of prior heavy or frequent use of the drug.
Green
A Richard
AR
Neuropharmacology Research Group, School of Pharmacy, De Montfort University, The Gateway, Leicester, LE1 9BH, UK. richard.green@astrazeneca.com
Sanchez
Veronica
V
O'Shea
Esther
E
Saadat
Kathryn S
KS
Elliott
J Martin
JM
Colado
M Isabel
MI
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006361:Heating; D007035:Hypothermia / Q000139:chemically induced*; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage* / Q000633:toxicity*; D051381:Rats; D018490:Serotonin Agents / Q000008:administration & dosage* / Q000633:toxicity*
D018490:Serotonin Agents; D018817:N-Methyl-3,4-methylenedioxyamphetamine