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Functional consequences of repeated (+/-)3,4-methylenedioxymethamphetamine (MDMA) treatment in rhesus monkeys
1Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA. mtaffe@scripps.edu
Abstract:
Six rhesus monkeys were trained to stable performance on neuropsychological tests of memory, reinforcer efficacy, reaction time and bimanual motor coordination. Three monkeys were then exposed to a high-dose, short course regimen of (+/-)3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") (4 days, 10 mg/kg i.m., b.i.d.). Following treatment, concentrations of 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) were reduced by approximately 50% in the treated animals, and this effect persisted for approximately three months post-MDMA. Behavioral performance was disrupted during acute MDMA treatment but returned to baseline within one week following treatment. MDMA also produced persistent alterations in late peak latencies of brainstem auditory evoked potentials (BSAEP), lasting three months post-MDMA. Both CSF 5-HIAA concentrations and evoked potential latencies were normalized four months after treatment. These findings indicate that serotonergic alterations associated with MDMA use may result in persisting changes in brain function.
Insights
This study investigated the effects of 3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") on rhesus monkeys. MDMA caused short-term behavioral disruptions and long-term changes in brain chemistry and function, specifically serotonin levels and auditory evoked potentials.
Area of Science:
- Neuroscience
- Pharmacology
- Primate Research
Background:
- 3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") is a psychoactive drug with known effects on serotonin systems.
- Understanding the long-term neurological consequences of MDMA exposure is crucial for public health and clinical practice.
Purpose of the Study:
- To investigate the persistent effects of a high-dose, short-term MDMA regimen on neurochemistry and neurophysiology in rhesus monkeys.
- To assess the duration of MDMA-induced alterations in cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) and brainstem auditory evoked potentials (BSAEP).
Main Methods:
- Six rhesus monkeys were trained on cognitive and motor tasks.
- Three monkeys received a high-dose, short-course regimen of MDMA (10 mg/kg i.m., b.i.d. for 4 days).
- CSF 5-HIAA levels and BSAEP were monitored, alongside behavioral performance, at various time points post-treatment.
Main Results:
- MDMA treatment significantly reduced CSF 5-HIAA concentrations by approximately 50%, an effect lasting for three months.
- Behavioral performance deficits during acute MDMA exposure resolved within one week post-treatment.
- Persistent alterations in BSAEP late peak latencies were observed for three months, normalizing at four months post-MDMA.
Conclusions:
- MDMA exposure can induce lasting serotonergic alterations in the brain.
- These neurochemical changes are associated with persistent functional modifications in neurophysiological measures, such as auditory evoked potentials.
- The findings suggest that MDMA use may lead to enduring changes in brain function.
