PMID- 29510210 OWN - NLM STAT- MEDLINE DCOM- 20190311 LR - 20190311 IS - 1873-7544 (Electronic) IS - 0306-4522 (Linking) VI - 377 DP - 2018 May 1 TI - 3,4-Methylenedioxymethamphetamine (MDMA) Alters Synaptic Dopamine Release in the Dorsal Striatum Through Nicotinic Receptors and DAT Inhibition. PG - 69-76 LID - S0306-4522(18)30162-3 [pii] LID - 10.1016/j.neuroscience.2018.02.037 [doi] AB - An increase of extracellular dopamine (DA) has been implicated in the psychostimulant properties of 3,4-methylenedioxymethamphetamine (MDMA). Although this drug has been reported to affect the DA uptake transporter (DAT), it might activate other mechanisms to regulate the outflow of DA in the brain. Our aim was to examine the overall effects of MDMA on the release of DA in the striatum. We studied the effect of MDMA on stimulus-evoked synaptic DA release in dorsal striatal slices of mice using in vitro amperometric techniques. We also tested the effects of MDMA on the nicotine-induced responses in substantia nigra pars compacta (SNpc) neurons using intracellular electrophysiological recordings. MDMA (1-30 microM) depressed the amplitude and prolonged the decay-time of synaptic DA release in the striatum. Interestingly, in the presence of the broad nicotinic receptor antagonist mecamylamine, and the more selective alpha(4)beta(2) antagonist dihydrobetaerythroidine (DHbetaE), MDMA enhanced both peak and duration of DA release. A similar effect was found on cocaine-insensitive (DAT-CI) mice slices. Concentrations of MDMA higher than 100 microM enhanced striatal DA outflow that was in turn, reduced by cocaine. Electrophysiological recordings of dopaminergic neurons in SNpc showed that MDMA depressed the effects of nicotine. Our data are consistent with a prevalent MDMA-induced inhibition of the synaptic release of DA in the dorsal striatum mediated by an interaction with nicotinic receptors. This drug also blocks DAT acting on a different site from cocaine and, at higher concentrations, has amphetamine-like releasing properties. CI - Copyright (c) 2018 IBRO. Published by Elsevier Ltd. All rights reserved. FAU - Rizzo, Francesca Romana AU - Rizzo FR AD - University of Rome 'Tor Vergata', 00133 Rome, Italy. FAU - Federici, Mauro AU - Federici M AD - IRCSS Fondazione Santa Lucia, 00143 Rome, Italy. FAU - Mercuri, Nicola Biagio AU - Mercuri NB AD - University of Rome 'Tor Vergata', 00133 Rome, Italy; IRCSS Fondazione Santa Lucia, 00143 Rome, Italy. Electronic address: mercurin@med.uniroma2.it. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180303 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Dopamine Plasma Membrane Transport Proteins) RN - 0 (Hallucinogens) RN - 0 (Receptors, Nicotinic) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) RN - VTD58H1Z2X (Dopamine) SB - IM MH - Animals MH - Corpus Striatum/*drug effects/metabolism MH - Dopamine/*metabolism MH - Dopamine Plasma Membrane Transport Proteins/*antagonists & inhibitors/genetics/metabolism MH - Dose-Response Relationship, Drug MH - Hallucinogens/*pharmacology MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology MH - Receptors, Nicotinic/*metabolism MH - Synapses/drug effects/metabolism MH - Tissue Culture Techniques OTO - NOTNLM OT - 3,4-methylenedioxymethamphetamine (MDMA) OT - DA transporter OT - cocaine OT - dopamine OT - nicotinic cholinergic receptors EDAT- 2018/03/07 06:00 MHDA- 2019/03/12 06:00 CRDT- 2018/03/07 06:00 PHST- 2017/09/22 00:00 [received] PHST- 2018/02/14 00:00 [revised] PHST- 2018/02/22 00:00 [accepted] PHST- 2018/03/07 06:00 [pubmed] PHST- 2019/03/12 06:00 [medline] PHST- 2018/03/07 06:00 [entrez] AID - S0306-4522(18)30162-3 [pii] AID - 10.1016/j.neuroscience.2018.02.037 [doi] PST - ppublish SO - Neuroscience. 2018 May 1;377:69-76. doi: 10.1016/j.neuroscience.2018.02.037. Epub 2018 Mar 3.