Acutely applied MDMA enhances long-term potentiation in rat hippocampus involving D1/D5 and 5-HT2 receptors through a polysynaptic mechanism.
Carlos Rozas, Sebastian Loyola, G Ugarte, Marc L Zeise, Miguel Reyes-Parada, Floria Pancetti, P Rojas, Bernardo Morales
European Neuropsychopharmacology August 2012 DOI: 10.1016/j.euroneuro.2011.11.010 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Ex vivo electrophysiological study in rat hippocampal slices Peer reviewed |
|---|---|
| Population | Hippocampal slices from young rats |
| Intervention | MDMA |
| Topics | MDMA Serotonin |
| Key points | Acute MDMA enhanced LTP at CA3-CA1 synapses without affecting LTD. The authors report that this enhancement involves presynaptic 5-HT2 serotonin receptors, postsynaptic D1/D5 dopamine receptors, and PKA-dependent signaling, and they propose a polysynaptic serotonergic-dopaminergic interaction as the mechanism, suggesting it may relate to MDMA-associated cognitive deficits. |
Abstract
3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a drug of abuse that induces learning and memory deficit. However, there are no experimental data that correlate the behavioral evidence with models of synaptic plasticity such as long-term potentiation (LTP) or long-term depression (LTD). Using field potential recordings in rat hippocampal slices of young rats, we found that acute application of MDMA enhances LTP in CA3-CA1 synapses without affecting LTD. Using specific antagonists and paired-pulse facilitation protocols we observed that the MDMA-dependent increase of LTP involves presynaptic 5-HT₂ serotonin receptors and postsynaptic D1/D5 dopamine receptors. In addition, the inhibition of PKA suppresses the MDMA-dependent increase in LTP, suggesting that dopamine receptor agonism activates cAMP-dependent intracellular pathways. We propose that MDMA exerts its LTP-altering effect involving a polysynaptic interaction between serotonergic and dopaminergic systems in hippocampal synapses. Our results are compatible with the view that the alterations in hippocampal LTP could be responsible for MDMA-dependent cognitive deficits observed in humans and animals.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
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- A Systematic Review of the MDMA Model to Address Social Impairment in Autism. Current Neuropharmacology 2021
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