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Methylenedioxymethamphetamine-induced hyperthermia and neurotoxicity are independently mediated by 5-HT2 receptors

Christopher J. Schmidt, Christine K. Black, Gina M. Abbate, Vicki L. Taylor

Brain Research October 1, 1990 DOI: 10.1016/0006-8993(90)90813-q (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Experimental study Peer reviewed
Population Rats
Interventions MDL 11 939 haloperidol MDL 27 777 reduced ambient temperature
Duration 1 week follow-up
Topics MDMA Serotonin
Keywords Neurochemical Hyperthermia Neurotoxicity Pharmacology Haloperidol Receptor antagonist
Citations 132
Key findings MDMA-induced hyperthermia and neurotoxicity can be dissociated, but hyperthermia may contribute to long-term neurochemical deficits.

Abstract

Methylenedioxymethamphetamine (MDMA) produced a significant hyperthermia in rats which was antagonized in a competitive manner by the selective 5-HT2 antagonist, MDL 11,939. The 5-HT antagonist also blocked MDMA-induced neurotoxicity as assessed by the decline in regional 5-HT concentrations observed 1 week later. These two effects of MDL 11,939 were dissociated at higher doses of MDMA where the antagonist still provided virtually complete protection against the neurochemical deficits but only partially attenuated the hyperthermic response. In contrast to the effect of the 5-HT2 antagonist, haloperidol did not alter MDMA-induced hyperthermia but did antagonize its long-term neurochemical effects. Similarly, coadministration of the selective 5-HT uptake inhibitor, MDL 27,777, did not affect the hyperthermia produced by a high dose of MDMA but completely prevented the depletion of 5-HT. When the MDMA-induced hyperthermia was prevented by temporarily maintaining animals at reduced ambient temperature, the neurochemical changes normally observed 1 week later were also blocked. Although these results demonstrate that the drugs tested do not antagonize MDMA-induced neurotoxicity by interfering with its effect on body temperature, they do indicate that MDMA-induced hyperthermia may contribute to the development of the drug's long-term neurochemical effects.

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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