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. 1995 Aug;115(7):1281–1289. doi: 10.1111/j.1476-5381.1995.tb15037.x

The hyperthermic and neurotoxic effects of 'Ecstasy' (MDMA) and 3,4 methylenedioxyamphetamine (MDA) in the Dark Agouti (DA) rat, a model of the CYP2D6 poor metabolizer phenotype.

M I Colado 1, J L Williams 1, A R Green 1
PMCID: PMC1908797  PMID: 7582557

Abstract

1. The effect of administration of 3,4-methylenedioxymethamphetamine (MDMA or 'Ecstasy') and its N-demethylated product, 3,4-methylenedioxyamphetamine (MDA) on both rectal temperature and long term neurotoxic loss of cerebral 5-hydroxytryptamine (5-HT) has been studied in male and female Dark Agouti (DA) rats. The female metabolizes debrisoquine more slowly than the male and its use has been suggested as a model of the human debrisoquine 4-hydroxylase poor metabolizer phenotype. 2. A novel h.p.l.c. method was developed and used to measure plasma MDMA and MDA concentrations in the DA rats. 3. The hyperthermic response following MDMA was enhanced in female rats. Plasma MDMA concentrations were also 57% higher than in males 45 min post-injection, while plasma concentrations of MDA were 48% lower. 4. Plasma concentrations of MDMA and MDA in male rats were unaffected by pretreatment with proadifen (15 mg kg-1) or quinidine (60 mg kg-1), but the hyperthermic response to MDMA (10 mg kg-1, i.p.) was enhanced by quinidine pretreatment. 5. The hyperthermic response following MDA was greater in male DA rats, despite plasma drug concentrations being 40% higher in females 60 min after injection. 6. Seven days after a single dose of MDMA (10 mg kg-1, i.p.) there was a substantial loss in the concentration of 5-HT and 5-hydroxyindoleacetic acid (5-HIA) in cortex and hippocampus. [3H]-paroxetine binding was also decreased by 27% in the cortex, indicating that the amine loss reflected a neurodegenerative change. MDMA (5 mg kg-1, i.p.) was without effect on brain 5-HT content.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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