Neurotoxic Effects of MDMA on Brain Serotonin Neurons: Evidence from Neurochemical and Radioligand Binding Studiesa
Errol B. de Souza, George Battaglia, Thomas R. Insel
Annals of the New York Academy of Sciences October 1, 1990 DOI: 10.1111/j.1749-6632.1990.tb16918.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Population | Rats and rhesus monkeys |
| Intervention | MDMA |
| Duration | Up to one year |
| Topics | Addiction MDMA Serotonin |
| Keywords | Neurochemical Drugs of abuse Library science |
| Citations | 54 |
| Key findings | MDMA administration causes dose-dependent, long-lasting degeneration of serotonin neurons in the brain, with greater potency in rhesus monkeys than rats, and functional recovery may be permanently impaired despite partial regeneration of uptake sites. |
Abstract
In summary, the data from both neurochemical and neuroanatomical studies demonstrate widespread and long-lasting degeneration of serotonin neurons in brain without any major or consistent effects on catecholamine neurons following in vivo administration of MDMA in both rats and rhesus monkeys. A detailed examination of the parameters involved in the neurotoxic and neurodegenerative effects of MDMA on brain serotonin neurons indicate that the severity of the lesion is dependent on the dose of drug administered with the drug being more potent in rhesus monkeys than in rats. Furthermore, the neurodegenerative effects of the drug are long-lasting (up to one year) with respect to neuronal regeneration (i.e. recovery of serotonin uptake sites) while functional recovery may be permanently impaired since serotonin content remains markedly (40-50%) below levels in age-matched controls for as long as one year after drug administration. The neurochemical and autoradiographic data suggest that there are some regional differences and morphological specificity to the neurodegenerative effects of MDMA as demonstrated by greater reductions in serotonin uptake sites in brain regions containing primarily terminals while regions containing axons of passage and cell bodies are relatively unaffected.
Comparable studies
Other preclinical and animal studies on MDMA for addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Reinforcing Effects of MDMA (‘Ecstasy’) in Drug-Naive and Cocaine-Trained Rats Rats | 2001 | Experimental study | |
| Enhancement of conditioned place preference response to cocaine in rats following subchronic administration of 3,4-methylenedioxymethamphetamine (MDMA) Male Sprague-Dawley rats | 2000 | Experimental study | |
| Contribution of impulsivity and novelty-seeking to the acquisition and maintenance of MDMA self-administration Rats | 2012 | Observational cohort | |
| Profile of MDMA Self-Administration from a Large Cohort of Rats: MDMA Develops a Profile of Dependence with Extended Testing Rats | 2012 | Observational cohort | n = 128 |
| Involvement of NMDA glutamate receptors in the acquisition and reinstatement of the conditioned place preference induced by MDMA Adolescent male mice | 2015 | Experimental study |
Citations in the library
Cited by 11
- Altered Serotonin Innervation Patterns in the Forebrain of Monkeys Treated with (±)3,4-Methylenedioxymethamphetamine Seven Years Previously: Factors Influencing Abnormal Recovery Journal of Neuroscience June 15, 1999
- Neurotoxicity of MDMA: Main effects and mechanisms. Experimental Neurology October 1, 2021
- Methylenedioxymethamphetamine (MDMA) in Psychiatry Journal of Clinical Psychopharmacology October 10, 2018
- Contribution of impulsivity and novelty-seeking to the acquisition and maintenance of MDMA self-administration Addiction Biology July 11, 2012
- MDMA-Based Psychotherapy in Treatment-Resistant Post-Traumatic Stress Disorder (PTSD): A Brief Narrative Overview of Current Evidence Diseases November 3, 2023
and 6 more in the library
Cites 10
- Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Journal of Neuroscience August 1, 1988
- Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Journal of Pharmacology and Experimental Therapeutics 1987
- 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. Journal of Pharmacology and Experimental Therapeutics September 1, 1987
- (±3,4-Methylenedioxymethamphetamine Selectively Damages Central Serotonergic Neurons in Nonhuman Primates JAMA July 1, 1988
- The Background and Chemistry of MDMA Journal of Psychoactive Drugs October 1, 1986
and 5 more in the library