Widespread reduction of dopamine cell bodies and terminals in adult rats exposed to a low dose regimen of MDMA during adolescence.
Cristina Cadoni, Augusta Pisanu, Nicola Simola, Lucia Frau, Pier Francesca Porceddu, Silvia Corongiu, Christian Dessì, Annesha Sil, Antonio Plumitallo, Jadwiga Wardas, Gaetano Di Chiara
Neuropharmacology September 1, 2017 DOI: 10.1016/j.neuropharm.2017.06.008 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled experimental animal study Peer reviewed |
|---|---|
| Population | Adolescent rats, assessed in adulthood |
| Interventions | MDMA Caffeine |
| Dose | MDMA 5 mg/kg for 10 days; caffeine 10 mg/kg |
| Duration | 10-day adolescent treatment, with assessment at adulthood |
| Topics | MDMA |
| Keywords | 3,4-methylendioxymethamphetamine pubchem cid Caffeine pubchem cid Neurotoxicity Nucleus accumbens Recognition memory Sensitization Tyrosine hydroxylase |
| Key findings | Adolescent exposure of rats to low-dose MDMA caused long-lasting reductions in dopamine neuron markers across the ventral tegmental area, substantia nigra, nucleus accumbens, and caudate-putamen, along with behavioral sensitization to an adult MDMA challenge, a potentiated dopamine increase in the nucleus accumbens core, and a recognition memory deficit. Caffeine co-administration did not affect these outcomes. The authors conclude this indicates a neurotoxic effect on dopamine neurons and suggest degeneration of those neurons. |
Abstract
Although MDMA (3,4-methylendioxymethamphetamine, ecstasy) neurotoxicity in serotonin neurons is largely recognized in a wide variety of species including man, neurotoxicity in dopamine (DA) neurons is thought to be species-specific. MDMA is mainly consumed by adolescents, often in conjunction with caffeine (Energy Drinks) and this association has been reported to exacerbate MDMA toxic effects. In order to model these aspects of MDMA use, vis-à-vis their impact on DA neurons, we investigated the effects of adolescent exposure to low doses of MDMA (5 mg/kg for 10 days), alone or in combination with caffeine (10 mg/kg) on neuronal and functional DA indices and on recognition memory in adult rats. MDMA reduced density of tyrosine hydroxylase (TH) positive neurons in the ventral tegmental area and in the substantia nigra pars compacta, and immunoreactivity of TH and DA transporter in the nucleus accumbens (NAc) shell and core, and caudate-putamen. This same treatment caused a reduction of basal dialysate DA in the NAc core. MDMA-pretreated rats also showed behavioral sensitization to a MDMA challenge at adulthood and potentiation of MDMA-induced increase of dialysate DA in the NAc core, but not in the NAc shell. In addition, MDMA-treated rats displayed a deficit in recognition memory. Caffeine co-administration did not affect the above outcomes. Our results show that adolescent exposure of rats to low doses of MDMA induces long-lasting and widespread reduction of DA neurons indicative of a neurotoxic effect on DA neurons and suggestive of a degeneration of the same neurons.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 12
- Neurotoxicity of MDMA: Main effects and mechanisms. Experimental Neurology October 1, 2021
- Increased iNOS and Nitrosative Stress in Dopaminergic Neurons of MDMA-Exposed Rats International Journal of Molecular Sciences March 12, 2019
- Brain dysfunctions and neurotoxicity induced by psychostimulants in experimental models and humans: an overview of recent findings Neural Regeneration Research February 22, 2024
- Characterization of the Neurochemical and Behavioral Effects of the Phenethylamine 2-Cl-4,5-MDMA in Adolescent and Adult Male Rats. The International Journal of Neuropsychopharmacology May 1, 2024
- Long-term neurocognitive side effects of MDMA in recreational ecstasy users following sustained abstinence: A systematic review and meta-analysis. Journal of Psychopharmacology November 19, 2025
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