3,4-Methylenedioxymethamphetamine (MDMA) Alters Synaptic Dopamine Release in the Dorsal Striatum Through Nicotinic Receptors and DAT Inhibition.
Francesca Romana Rizzo, Mauro Federici, Nicola Biagio Mercuri
Neuroscience May 1, 2018 DOI: 10.1016/j.neuroscience.2018.02.037 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro experimental study Peer reviewed |
|---|---|
| Population | Mouse dorsal striatal slices and substantia nigra pars compacta neurons |
| Interventions | MDMA mecamylamine dihydroβerythroidine (DHβE) cocaine nicotine |
| Dose | 1-30 µM; higher than 100 µM |
| Topics | MDMA |
| Keywords | 3,4-Methylenedioxymethamphetamine MDMA Da transporter Cocaine Dopamine Nicotinic cholinergic receptors |
| Key findings | MDMA (1-30 µM) depressed the amplitude and prolonged the decay of stimulus-evoked synaptic dopamine release in mouse dorsal striatum, but enhanced release when nicotinic receptors were blocked or in cocaine-insensitive DAT-CI mice. Above 100 µM, MDMA increased dopamine outflow, which cocaine reduced. The authors conclude MDMA predominantly inhibits synaptic dopamine release via nicotinic receptor interaction, blocks DAT at a site different from cocaine, and has amphetamine-like releasing properties at high concentrations. |
Abstract
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 µM) 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 α4β2 antagonist dihydroβerythroidine (DHβE), 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 µM 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.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 4
- Psychedelics and Reward Processing: Before and After the 1970 Controlled Substances Act Psychedelic Medicine July 24, 2026
- Increased response to 3,4 methylenedioxymethamphetamine (MDMA) reward and altered gene expression in zebrafish during short- and long-term nicotine withdrawal Molecular Neurobiology November 24, 2020
- The Acute Toxic and Neurotoxic Effects of 3,4-methylenedioxymethamphetamine are More Pronounced in Adolescent than Adult Mice Behavioural Brain Research December 3, 2019
- Of mice and men on MDMA: a translational comparison of the neuropsychobiological effects of 3,4-methylenedioxymethamphetamine ('Ecstasy'). Brain Research November 14, 2019
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