Original Article| Volume 62, ISSUE 6, P680-686, September 15, 2007

Electrophysiologic Changes in Ventral Midbrain Dopaminergic Neurons Resulting from (+/−) -3,4-Methylenedioxymethamphetamine (MDMA—“Ecstasy”)

  • Mauro Federici
    Laboratory of Experimental Neurology, Fondazione Santa Lucia—IRCCS and Neurological Clinic, University of Rome Tor Vergata, Rome, Italy.
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  • Luca Sebastianelli
    Laboratory of Experimental Neurology, Fondazione Santa Lucia—IRCCS and Neurological Clinic, University of Rome Tor Vergata, Rome, Italy.
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  • Silvia Natoli
    Laboratory of Experimental Neurology, Fondazione Santa Lucia—IRCCS and Neurological Clinic, University of Rome Tor Vergata, Rome, Italy.
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  • Giorgio Bernardi
    Laboratory of Experimental Neurology, Fondazione Santa Lucia—IRCCS and Neurological Clinic, University of Rome Tor Vergata, Rome, Italy.
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  • Nicola B. Mercuri
    Address reprint requests to Nicola B. Mercuri, M.D., Laboratory of Experimental Neurology, Fondazione Santa Lucia—Centro Europeo di Ricerca sul Cervello (CERC) Via del Fosso di Fiorano, 64-00142 Roma, Italy
    Laboratory of Experimental Neurology, Fondazione Santa Lucia—IRCCS and Neurological Clinic, University of Rome Tor Vergata, Rome, Italy.
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      Although dopamine (DA) has been implicated in the psychostimulant properties of 3,4-methylenedioxymethamphetamine (MDMA), there is no detailed information on its modalities of action on single ventral midbrain dopaminergic neurons.


      We examined the actions of MDMA on intracellularly recorded dopaminergic neurons maintained in slices.


      At 1 μmol/L, MDMA depolarized and excited the cells; at 3 μmol/L, either excited or inhibited the neurons. Interestingly, higher concentrations (10–30 μmol/L) inhibited firing through membrane hyperpolarization or caused an outward current. Whereas MDMA’s excitatory effects were antagonized by pindolol, indicating involvement of 5-HT 1B receptors, the inhibitory effects were counteracted by sulpiride indicating involvement D2 receptors. Treatment of the cells with carbidopa eliminated MDMA-induced firing inhibition and membrane hyperpolarization. MDMA enhanced DA-induced cellular responses but reduced those of amphetamine. Cocaine-induced outward currents were not affected by MDMA. These actions are consistent with inhibition of the DA transporter. Moreover, MDMA depressed the GABAB IPSP by activating 5-HT 1B receptors.


      Our data demonstrate that 3–30 μmol/L MDMA preferentially inhibits the dopaminergic cells via indirect activation of D2 autoreceptors due to increased extracellular concentration of DA. In contrast, reduction of the GABAB IPSP could partially account for excitation caused by 1–3 μmol/L drug.

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