Chronic administration of amphetamines disturbs development of neural progenitor cells in young adult nonhuman primates.
Rahul R Dutta, Michael A. Taffe, Chitra D Mandyam
Progress in Neuro-Psychopharmacology and Biological Psychiatry July 13, 2018 DOI: 10.1016/j.pnpbp.2018.03.023 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Population | Young adult rhesus macaques |
| Interventions | MDMA MDA and methamphetamine |
| Duration | 9.6 months of intermittent exposure |
| Measures | Ki-67, NeuroD1 |
| Topics | MDMA |
| Keywords | Granule cell neurons Hippocampus Ki-67 Methamphetamine Neurod1 |
| Key findings | Intermittent exposure to MDMA alone or to MDMA, MDA, and methamphetamine over 9.6 months was associated with more than an 80% decrease in dividing Ki-67 cells and more than a 50% decrease in NeuroD1 cells in the hippocampus. Apoptosis and granule cell neuron numbers were unchanged, which the authors interpret as selective interference with the generation and maturation of newly born granule cell neurons. |
Abstract
The detrimental effects of amphetamines on developmental stages of NPCs are limited to rodent brain and it is not known if these effects occur in nonhuman primates which are the focus of the current investigation. Young adult rhesus macaques either experienced MDMA only, a combination of amphetamines (MDMA, MDA and methamphetamine) or no amphetamines (controls) and hippocampal tissue was processed for immunohistochemical analysis.Quantitative stereological analysis showed that intermittent exposure to MDMA or the three amphetamines over 9.6 months causes >80% decrease in the number of Ki-67 cells (actively dividing NPCs) and >50% decrease in the number of NeuroD1 cells (NPCs that have attained a neuronal phenotype). Co-labeling analysis revealed distinct, actively dividing hippocampal NPCs in the subgranular zone of the dentate gyrus that were in transition from stem-like radial glia-like cells (type-1) to immature transiently amplifying neuroblasts (type-2a, type-2b, and type-3).MDMA-alone and the combination reduced the number of dividing type-1 and type-3 NPCs and cells that were not NPCs. These data indicate that amphetamines interfere with the division and migration of NPCs. Notably, the reduction in the number of NPCs and immature neurons were not associated with changes in cell death (via apoptosis) or granule cell neuron numbers, indicating that amphetamines selectively affected the generation and maturation of newly born granule cell neurons. In sum, our findings suggest that alterations in the cellular composition in the dentate gyrus during chronic exposure to amphetamines can effect neuroplasticity in the hippocampus and influence functional properties of hippocampal neurons.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cites 8
- Psychedelics and the Human Receptorome PLoS One 2010
- RETRACTED: Severe Dopaminergic Neurotoxicity in Primates After a Common Recreational Dose Regimen of MDMA ("Ecstasy") Science September 27, 2002
- Correction: Psychedelics and the Human Receptorome PLoS One March 4, 2010
- MDMA and 5‐HT neurotoxicity: the empirical evidence for its adverse effects in humans – no need for translation British Journal of Pharmacology March 9, 2012
- Comparative effects of amphetamine-like psychostimulants on rat hippocampal cell genesis at different developmental ages. Neurotoxicology September 2016
and 3 more in the library