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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

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Abstract

Rationale

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°C) and high (30°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°C and 30°C.

Results

MDMA (5 mg/kg IP) produced a sustained hyperthermic response in rats housed at 30°C, but not in rats housed at 19°C. A prior (5 weeks earlier) neurotoxic dose of MDMA (12.5 mg/kg IP) resulted in MDMA (5 mg/kg) producing a greater hyperthermic response in rats housed at 30°C than in non-pre-treated animals. Repeated MDMA administration (binge dosing; 2, 4 or 6 mg/kg ×3) produced dose-dependent hyperthermia in rats housed at 19°C, with MDMA (2 mg/kg ×3) having little effect. However, this dose produced significant hyperthermia (≥2°C above control values)in rats housed at 30°C following the third dose. A prior neurotoxic dose of MDMA resulted in MDMA (2 mg/kg ×3) producing marked hyperthermia (>1°C) after the first dose and severe hyperthermia (≥2°C) after the third dose.

Conclusions

MDMA administration to rats housed at 30°C produces a more severe hyperthermic response than that seen in rats housed at 19°C. A prior neurotoxic dose enhances the response further in animals housed at 30°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.

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Authors and Affiliations

  1. Neuropharmacology Research Group, School of Pharmacy, De Montfort University, The Gateway, Leicester, LE1 9BH, UK

    A. Richard Green, Kathryn S. Saadat & J. Martin Elliott

  2. Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense, 28040, Madrid, Spain

    Veronica Sanchez, Esther O’Shea & M. Isabel Colado

  3. AstraZeneca R&D Charnwood, Bakewell Road, Loughborough , LE11 5RH, UK

    A. Richard Green

Authors
  1. A. Richard Green
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  2. Veronica Sanchez
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  3. Esther O’Shea
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  4. Kathryn S. Saadat
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  5. J. Martin Elliott
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  6. M. Isabel Colado
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Correspondence to A. Richard Green.

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Green, A.R., Sanchez, V., O’Shea, E. et al. 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. Psychopharmacology 173, 264–269 (2004). https://doi.org/10.1007/s00213-003-1725-2

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  • DOI: https://doi.org/10.1007/s00213-003-1725-2

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