Gene expression analysis indicates reduced memory and cognitive functions in the hippocampus and increase in synaptic reorganization in the frontal cortex 3 weeks after MDMA administration in Dark Agouti rats.
Peter Petschner, Viola Tamasi, Csaba Ádori, Eszter Kirilly, Rómeó D. Andó, Laszlo Tothfalusi, György Bagdy
BMC Genomics August 2, 2018 DOI: 10.1186/s12864-018-4929-x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study Peer reviewed |
|---|---|
| Population | Dark Agouti rats |
| Intervention | MDMA |
| Dose | 15 mg/kg |
| Duration | 3 weeks after a single dose |
| Measures | Illumina RatRef bead arrays |
| Topics | MDMA Serotonin |
| Keywords | Cb1 Camkii Endocannabinoid Eph receptors Gene expression Microarray Nmda2b Rhogtpase |
| Key findings | A single neurotoxic dose of MDMA (15 mg/kg) in Dark Agouti rats altered gene expression in the hippocampus, frontal cortex, and dorsal raphe three weeks later, with the most pronounced changes in the hippocampus. The authors propose that downregulation of synaptic plasticity and long-term potentiation pathways in the hippocampus may underlie cognitive deficits in MDMA users, while upregulated synapse assembly genes in the frontal cortex suggest possible synaptic reorganization, which they argue may relate to MDMA's therapeutic effects in PTSD. |
Abstract
3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is a widely used entactogenic drug known to impair cognitive functions on the long-run. Both hippocampal and frontal cortical regions have well established roles in behavior, memory formation and other cognitive tasks and damage of these regions is associated with altered behavior and cognitive functions frequently described in otherwise healthy MDMA users. Meanwhile, in post-traumatic stress disorder (PTSD) patients seem to benefit from therapeutic application of the drug, where damage in hippocampal cue extinction may play a role. The aim of this study was to examine the hippocampus, frontal cortex and dorsal raphe of Dark Agouti rats with gene expression arrays (Illumina RatRef bead arrays) looking for possible mechanisms and new candidates contributing to the consequences of a single dose of MDMA (15 mg/kg) 3 weeks earlier. The number of differentially expressed genes in the hippocampus, frontal cortex and the dorsal raphe were 481, 155, and 15, respectively. Gene set enrichment analysis of the microarray data revealed reduced expression of 'memory' and 'cognition', 'dendrite development' and 'regulation of synaptic plasticity' gene sets in the hippocampus, parallel to the downregulation of CaMK II subunits, glutamate-, CB1 cannabinoid- and EphA4, EphA5, EphA6 receptors. Downregulated gene sets in the frontal cortex were related to protein synthesis, chromatin organization, transmembrane transport processes, while 'dendrite development', 'regulation of synaptic plasticity' and 'positive regulation of synapse assembly' gene sets were upregulated besides elevated levels of a CaMK II subunit and NMDA2B glutamate receptor. Changes in the dorsal raphe region were mild and in most cases not significant. The present data raise the possibility of new synapse formation / synaptic reorganization in the frontal cortex 3 weeks after a single neurotoxic dose of MDMA. In contrast, a prolonged depression of new neurite formation in the hippocampus is proposed by downregulations of members in long-term potentiation pathway and synaptic plasticity emphasizing the particular vulnerability of this brain region and proposing a mechanism responsible for cognitive problems in healthy individuals. At the same time, these results underpin benefits of MDMA in PTSD, where the drug may help memory extinction.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 7
- Increased iNOS and Nitrosative Stress in Dopaminergic Neurons of MDMA-Exposed Rats International Journal of Molecular Sciences March 12, 2019
- The functional connectome of 3,4‐methyldioxymethamphetamine‐related declarative memory impairments Human Brain Mapping August 2, 2023
- 3,4-Methylenedioxymethamphetamine (MDMA) - Assisted psychotherapy for treatment of posttraumatic stress disorder: Literature review Romanian Journal of Psychiatry & Psychotherapy March 31, 2020
- MDMA for the treatment of misophonia, a proposal. Frontiers in Psychiatry November 10, 2022
- Brain-derived neurotrophic factor protects serotonergic neurons against 3,4-methylenedioxymethamphetamine (“Ecstasy”) induced cytoskeletal damage Journal of Neural Transmission June 1, 2022
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