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Effect of Repeated (‘Binge’) Dosing of MDMA to Rats Housed at Normal and High Temperature on Neurotoxicdamage to Cerebral 5-Ht and Dopamine Neurones

Esther O’shea

Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense, Madrid, Spain

Kathryn S. Saadat

J. Martin Elliott

Neuropharmacology Research Group, School of Pharmacy, De Montfort University, The Gateway, Leicester, UK

M. Isabel Colado

Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense, Madrid, Spain

A. Richard Green

Neuropharmacology Research Group, School of Pharmacy, De Montfort University, The Gateway, Leicester and Astra Zeneca R&D Charnwood, Loughborough, UKrichard.green{at}astrazeneca.com

The technique of ‘binge’ dosing (several doses in one session) by recreational users of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) requires evaluation in terms of its consequences on the acute hyperthermic response and long-term neurotoxicity. We examined the neurotoxic effects of this dosing schedule on 5-HT and dopamineneurones in the rat brain. When repeated (three) doses of MDMA (2, 4 and 6 mg/kg i.p.) were given 3 h apart to rats housed at 19 °C, a dose-dependent acute hyperthermia and long-term loss of 5-HT was observed in several brain regions (hippocampus, cortex and striatum), with an approximate 50% loss following 3 x 4mg/kg and 65% decrease following 3 x 6mg/kg. No decrease in striatal dopamine content was detected. When MDMA (4 mg/kg i.p.) was given repeatedly to rats housed at 30 °C, a larger acute hyperthermic response than that observed in rats treated at 19 °C environment was seen (maximum response 2.6 ± 0.1 °C versus 1.3 ± 0.2 °C). A long-term cerebral 5-HT loss of approximately 65% was also detected in both the cortex and hippocampus, but no loss in striatal dopamine content occurred. These data emphasize the increased acute hyperthermic response and neurotoxicity which occurs when MDMA is administered in a hot room environment compared to normal room temperature conditions, and support the view that MDMA is a selective 5-HT neurotoxin, even when a binge dosing schedule is employed and the rats are present in a hot environment.

Key Words: binge dosing • dopamine • ecstasy • 5-hydroxytryptamine • hyperthermia • 3,4-methylenedioxymethamphetamine • room temperature

Journal of Psychopharmacology, Vol. 18, No. 3, 412-416 (2004)
DOI: 10.1177/026988110401800312


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