Effects of MDMA on neuroplasticity, amyloid burden and phospho-tau expression in APPswe/PS1dE9 mice.
Sonia Abad, Carla Ramon-Duaso, Raúl López‐arnau, Jaume Folch, David Pubill, Jordi Camarasa, Antoni Camins, Elena Escubedo
Journal of Psychopharmacology September 2019 DOI: 10.1177/0269881119855987 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study in a transgenic mouse model Peer reviewed |
|---|---|
| Population | Transgenic APP/PS1 dE9 mice modeling presymptomatic familial Alzheimer's disease and wild-type mice |
| Intervention | MDMA |
| Topics | MDMA Neuroplasticity |
| Keywords | Alzheimer’s disease Amyloid plaques Memory Mouse model |
| Key findings | Chronic MDMA treatment caused recognition memory deficits in both genotypes and significantly increased cortical amyloid plaques, Aβ40, Aβ42, and secreted APPβ levels in transgenic mice, with elevated tau phosphorylation (S199) that did not appear to involve AKT, CDK5, or GSK3β. The authors state these results support previous evidence that MDMA can contribute to the amyloid cascade. |
Abstract
3,4-Methylenedioxymethamphetamine (MDMA) is still one of the most consumed drugs by adolescents. Its abuse is related with cognitive impairment, which seems due to maladaptive plasticity and neural stress. In turn, new hypotheses suggest that Alzheimer's disease (AD) may be promoted by neural stressors. To test if there is an increase in vulnerability to AD after chronic MDMA consumption, we investigated the effects of this drug on recognition memory and its neurotoxic and neuroplastic effects in a transgenic mouse model of presymptomatic familiar AD (APP/PS1 dE9, Tg). MDMA-treated animals showed recognition memory deficits, regardless of genotype, which were accompanied by changes in plasticity markers. Tg mice showed an impaired expression of Arc compared with wild-type animals, but exposure to MDMA induced an increase in the expression of this factor of the same percentage in both genotypes. However, the expression of c-fos, BDNF and p-CREB was not significantly altered by MDMA treatment in Tg mice. Although Tg mice had higher free choline levels than wild-type mice (about 123%), MDMA did not modify these levels in any case, ruling out any specific effect of this drug on the acetylcholine pathway. MDMA treatment significantly increased the presence of cortical amyloid plaques, as well as Aβ40, Aβ42 and secreted APPβ levels in Tg mice. These plaques were accompanied by increased tau phosphorylation (S199), which does not seem to occur via the canonic pathway involving AKT, CDK5 or GSK3β. The present results support previous evidences that MDMA can contribute to the amyloid cascade.
Comparable studies
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| The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro Progenitor cells from subventricular and subgranular zones of adult mice brains | 2017 | In vitro experimental study | |
| N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo Mice | 2020 | In vitro and in vivo experimental study |
Citations in the library
Cited by 3
- MDMA administration attenuates hippocampal IL-β immunoreactivity and subsequent stress-enhanced fear learning: An animal model of PTSD Brain, Behavior, & Immunity - Health October 1, 2022
- Exploring the impact of MDMA and oxytocin ligands on anxiety and social responses: A comprehensive behavioural and molecular study in the zebrafish model. Journal of Psychopharmacology April 1, 2025
- Neuronal and peripheral damages induced by synthetic psychoactive substances: an update of recent findings from human and animal studies. Neural Regeneration Research May 1, 2020
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