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Evidence that both intragastric and subcutaneous administration of methylenedioxymethylamphetamine (MDMA) produce serotonin neurotoxicity in rhesus monkeys.

M S Kleven, William L. Woolverton, Lewis S. Seiden

Brain Research May 29, 1989 DOI: 10.1016/0006-8993(89)90700-2 (opens in new tab)

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AI-extracted from the abstract
Characteristics Experimental animal study Peer reviewed
Population Rhesus monkeys
Intervention MDMA
Dose 5.0 mg/kg/12 h x 4 days
Duration 4 days of dosing; assessed 2 weeks after the last injection
Measures serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), [3H]5-HT uptake sites
Topics MDMA Serotonin
Key findings Repeated MDMA (5.0 mg/kg every 12 hours for 4 days) by intragastric or subcutaneous routes depleted serotonin and 5-HIAA in several brain regions two weeks after the last injection. Hippocampal [3H]5-HT uptake sites fell significantly in intragastrically treated monkeys; the subcutaneous group's reduction did not reach statistical significance. The authors suggest repeated MDMA produces long-lasting, potentially neurotoxic effects on central serotonin neurons in primates, including by the oral route.

Abstract

It has been demonstrated that repeated, subcutaneous administration of 3,4-methylenedioxymethamphetamine (MDMA) to rats, guinea pigs, and squirrel monkeys produces long-lasting depletions of serotonin (5-hydroxytryptamine; 5-HT) in several brain regions. Since evidence of degenerating 5-HT neurons has been observed in the rat brain following MDMA injections, it is likely that these depletions are due to neurotoxicity similar to that observed with other substituted amphetamines. The purpose of the present study was to determine if MDMA produces similar evidence of neurotoxicity in rhesus monkeys when administered by either the intragastric (i.g.) or subcutaneous (s.c.) route. Administration of MDMA (5.0 mg/kg/12 h x 4 days) by either i.g. or s.c. routes depleted 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in various brain regions 2 weeks after the last injection. Further, a significant decrease in [3H]5-HT uptake sites in the hippocampus was observed in monkeys treated with MDMA by the i.g. route. Reductions in uptake sites did not achieve statistical significance when drug was administered s.c. The results suggest that repeated administration of MDMA produces long-lasting, potentially neurotoxic effects on central 5-HT neurons in primates and does so when given orally.

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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MDMA Serotonin