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MDMA modulates spontaneous firing of subthalamic nucleus neurons in vitro

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Abstract

3,4-Methylene-dioxy-N-methylamphetamine (MDMA, ‘ecstasy’) has a broad spectrum of molecular targets in the brain, among them receptors and transporters of the serotonergic (5-hydroxytryptamine, 5-HT) and noradrenergic systems. Its action on the serotonergic system modulates motor systems in rodents and humans. Although parts of the basal ganglia could be identified as mediators of the motor effects of MDMA, very little is known about the role of the subthalamic nucleus (STN). Therefore, this study investigated the modulation of spontaneous action potential activity of the STN by MDMA (2.5–20 µM) in vitro. MDMA had very heterogeneous effects, ranging from a complete but reversible inhibition to a more than twofold increase in firing at 5 µM. On average, MDMA excited STN neurons moderately, but lost its excitatory effect in the presence of the 5-HT2A antagonist MDL 11,939. 5-HT1A receptors did not appear to play a major role. Effects of MDMA on transporters for serotonin (SERT) and norepinephrine (NET) were investigated by coapplication of the reuptake inhibitors citalopram and desipramine, respectively. Similar to the effects of 5-HT2A receptor blockade, antagonism of SERT and NET bestowed an inhibitory effect on MDMA. From these results, we conclude that both the 5-HT and the noradrenergic system mediate MDMA-induced effects on STN neurons.

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Acknowledgments

We are indebted to Ulrich Nagel for the kind gift of MDMA, and thank Christine Pedroarena for providing us with 5-HT and Bernd Antkowiak for valuable discussion of the manuscript.

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Authors and Affiliations

  1. Experimental Anaesthesiology Section, University Hospital Tübingen, Waldhörnlestr. 22, 72072, Tübingen, Germany

    Luise Liebig & Harald Hentschke

  2. Neuropharmacology, Institute of Neurobiology, University of Tübingen, Tübingen, Germany

    Luise Liebig & Andreas von Ameln-Mayerhofer

  3. Graduate School of Neural and Behavioural Sciences, International Max-Planck Research School, University of Tübingen, Tübingen, Germany

    Luise Liebig

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  1. Luise Liebig
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Liebig, L., von Ameln-Mayerhofer, A. & Hentschke, H. MDMA modulates spontaneous firing of subthalamic nucleus neurons in vitro. Exp Brain Res 233, 137–147 (2015). https://doi.org/10.1007/s00221-014-4095-6

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