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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

Verónica Sánchez, Esther O’shea, Kathryn S. Saadat, J.m. Elliott, María Isabel Colado, Alfred Richard Green

Journal of Psychopharmacology September 1, 2004 DOI: 10.1177/026988110401800312 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Animal experiment Peer reviewed
Population Rats
Intervention MDMA
Dose 2, 4 and 6 mg/kg i.p.
Duration Acute and long-term (no specific follow-up duration stated)
Topics MDMA Serotonin
Keywords Dopamine Neurotoxicity Dosing Hyperthermia Striatum Hippocampus Anesthesia Endocrinology Pharmacology
Citations 66
Key findings Binge dosing of MDMA in rats causes dose-dependent hyperthermia and selective long-term loss of serotonin in multiple brain regions, with no loss of dopamine, and this neurotoxicity is worsened by a hot environment.

Abstract

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 × 4mg/kg and 65% decrease following 3 × 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.

Comparable studies

Other preclinical and animal studies on MDMA, most cited first.

Study Year Design Participants
Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) 1987 Experimental study
3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain 1987 Animal experiment
Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells 2006 In vitro laboratory study
Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat Rats 1998 Experimental study
Altered Serotonin Innervation Patterns in the Forebrain of Monkeys Treated with (±)3,4-Methylenedioxymethamphetamine Seven Years Previously: Factors Influencing Abnormal Recovery Squirrel monkeys treated with MDMA 1999 Observational cohort

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