Journal
EUROPEAN NEUROPSYCHOPHARMACOLOGY
Volume 22, Issue 8, Pages 584-595Publisher
ELSEVIER
DOI: 10.1016/j.euroneuro.2011.11.010
Keywords
MDMA; 5-HT; DA; Hippocampus; LTP; LTD
Funding
- FONDECYT [1080652]
- PBCT-CONICYT [79090013]
- DICYT of University of Santiago de Chile [2070724]
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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 LIP-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. (C) 2011 Elsevier B.V. and ECNP. All rights reserved.
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