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Repeated exposure to MDMA triggers long-term plasticity of noradrenergic and serotonergic neurons

Molecular Psychiatry volume 19, pages 823–833 (2014)Cite this article

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Abstract

3,4-Methylenedioxymethamphetamine (MDMA or ‘ecstasy’) is a psychostimulant drug, widely used recreationally among young people in Europe and North America. Although its neurotoxicity has been extensively described, little is known about its ability to strengthen neural circuits when administered in a manner that reproduces human abuse (i.e. repeated exposure to a low dose). C57BL/6J mice were repeatedly injected with MDMA (10 mg kg−1, intraperitoneally) and studied after a 4-day or a 1-month withdrawal. We show, using in vivo microdialysis and locomotor activity monitoring, that repeated injections of MDMA induce a long-term sensitization of noradrenergic and serotonergic neurons, which correlates with behavioral sensitization. The development of this phenomenon, which lasts for at least 1 month after withdrawal, requires repeated stimulation of α1B-adrenergic and 5-hydroxytryptamine (5-HT)2A receptors. Moreover, behavioral and neuroendocrine assays indicate that hyper-reactivity of noradrenergic and serotonergic networks is associated with a persistent desensitization of somatodendritic α2A-adrenergic and 5-HT1A autoreceptor function. Finally, molecular analysis including radiolabeling, western blot and quantitative reverse transcription-polymerase chain reaction reveals that mice repeatedly treated with MDMA exhibit normal α2A-adrenergic and 5-HT1A receptor binding, but a long-lasting downregulation of Gαi proteins expression in both locus coeruleus and dorsal raphe nucleus. Altogether, our results show that repeated MDMA exposure causes strong neural and behavioral adaptations and that inhibitory feedback mediated by α2A-adrenergic and 5-HT1A autoreceptors has an important role in the physiopathology of addictive behaviors.

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References

  1. Ricaurte G, Bryan G, Strauss L, Seiden L, Schuster C . Hallucinogenic amphetamine selectively destroys brain serotonin nerve terminals. Science 1985; 229: 986–988.

    Article  CAS  PubMed  Google Scholar 

  2. McCann UD, Szabo Z, Scheffel U, Dannals RF, Ricaurte GA . Positron emission tomographic evidence of toxic effect of MDMA (‘Ecstasy’) on brain serotonin neurons in human beings. Lancet 1998; 352: 1433–1437.

    Article  CAS  PubMed  Google Scholar 

  3. Urban NB, Girgis RR, Talbot PS, Kegeles LS, Xu X, Frankle WG et al. Sustained recreational use of ecstasy is associated with altered pre and postsynaptic markers of serotonin transmission in neocortical areas: a PET study with [C]DASB and [C]MDL 100907. Neuropsychopharmacology 2012; 37: 1465–1473.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Schifano F . Chronic atypical psychosis associated with MDMA (‘ecstasy’) abuse. Lancet 1991; 338: 1335.

    Article  CAS  PubMed  Google Scholar 

  5. Benazzi F, Mazzoli M . Psychiatric illness associated with ‘ecstasy’. Lancet 1991; 338: 1520.

    Article  CAS  PubMed  Google Scholar 

  6. Scott RM, Hides L, Allen JS, Burke R, Lubman DI . Depressive and anxiety symptomatology in ecstasy users: the relative contribution of genes, trauma, life stress and drug use. Psychopharmacology (Berl) 2010; 209: 25–36.

    Article  CAS  Google Scholar 

  7. Nutt D, King LA, Saulsbury W, Blakemore C . Development of a rational scale to assess the harm of drugs of potential misuse. Lancet 2007; 369: 1047–1053, review.

    Article  PubMed  Google Scholar 

  8. Gold LH, Koob GF . MDMA produces stimulant-like conditioned locomotor activity. Psychopharmacology (Berl) 1989; 99: 352–356.

    Article  CAS  Google Scholar 

  9. Kalivas PW, Duffy P, White SR . MDMA elicits behavioral and neurochemical sensitization in rats. Neuropsychopharmacology 1998; 18: 469–479.

    Article  CAS  PubMed  Google Scholar 

  10. Doly S, Bertran-Gonzalez J, Callebert J, Bruneau A, Banas SM, Belmer A et al. Role of serotonin via 5-HT2B receptors in the reinforcing effects of MDMA in mice. PLoS One 2009; 4: e7952.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Robinson TE, Berridge KC . The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Brain Res Rev 1993; 18: 247–291.

    Article  CAS  PubMed  Google Scholar 

  12. Robinson TE, Berridge KC . The psychology and neurobiology of addiction: an incentive-sensitization view. Addiction 2000; 95 (Suppl 2): S91–117.

    PubMed  Google Scholar 

  13. Nestler EJ, Aghajanian GK . Molecular and cellular basis of addiction. Science 1997; 278: 58–63, review.

    Article  CAS  PubMed  Google Scholar 

  14. Nestler EJ . Is there a common molecular pathway for addiction? Nat Neurosci 2005; 8: 1445–1449, review.

    Article  CAS  PubMed  Google Scholar 

  15. Di Chiara G, Imperato A . Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci USA 1988; 85: 5274–5278.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Pontieri FE, Tanda G, Orzi F, Di Chiara G . Effects of nicotine on the nucleus accumbens and similarity to those of addictive drugs. Nature 1996; 382: 255–257.

    Article  CAS  PubMed  Google Scholar 

  17. Tanda G, Pontieri FE, Di Chiara G . Cannabinoid and heroin activation of mesolimbic dopamine transmission by a common mu1 opioid receptor mechanism. Science 1997; 276: 2048–2050.

    Article  CAS  PubMed  Google Scholar 

  18. Cadoni C, Solinas M, Pisanu A, Zernig G, Acquas E, Di Chiara G . Effect of 3,4-methylendioxymethamphetamine (MDMA, ‘ecstasy’) on dopamine transmission in the nucleus accumbens shell and core. Brain Res 2005; 1055: 143–148.

    Article  CAS  PubMed  Google Scholar 

  19. Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI et al. Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse 2001; 39: 32–41.

    Article  CAS  PubMed  Google Scholar 

  20. Han DD, Gu HH . Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs. BMC Pharmacol 2006; 6: 6.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Verrico CD, Miller GM, Madras BK . MDMA (Ecstasy) and human dopamine, norepinephrine, and serotonin transporters: implications for MDMA-induced neurotoxicity and treatment. Psychopharmacology (Berl) 2007; 189: 489–503.

    Article  CAS  Google Scholar 

  22. Selken J, Nichols DE . Alpha1-adrenergic receptors mediate the locomotor response to systemic administration of (+/−)-3,4-methylenedioxymethamphetamine (MDMA) in rats. Pharmacol Biochem Behav 2007; 86: 622–630.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Herin DV, Liu S, Ullrich T, Rice KC, Cunningham KA . Role of the serotonin 5-HT2A receptor in the hyperlocomotive and hyperthermic effects of (+)-3,4-methylenedioxymethamphetamine. Psychopharmacology (Berl) 2005; 178: 505–513.

    Article  CAS  Google Scholar 

  24. Trigo JM, Renoir T, Lanfumey L, Hamon M, Lesch KP, Robledo P et al. 3,4-methylenedioxymethamphetamine self-administration is abolished in serotonin transporter knockout mice. Biol Psychiatry 2007; 62: 669–679.

    Article  CAS  PubMed  Google Scholar 

  25. Orejarena MJ, Lanfumey L, Maldonado R, Robledo P . Involvement of 5-HT2A receptors in MDMA reinforcement and cue-induced reinstatement of MDMA-seeking behavior. Int J Neuropsychopharmacol 2010; 14: 1–14.

    Google Scholar 

  26. Salomon L, Lanteri C, Glowinski J, Tassin JP . Behavioral sensitization to amphetamine results from an uncoupling between noradrenergic and serotonergic neurons. Proc Natl Acad Sci USA 2006; 103: 7476–7481.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Lanteri C, Salomon L, Torrens Y, Glowinski J, Tassin JP . Drugs of abuse specifically sensitize noradrenergic and serotonergic neurons via a non-dopaminergic mechanism. Neuropsychopharmacology 2008; 33: 1724–1734.

    Article  CAS  PubMed  Google Scholar 

  28. Lanteri C, Hernández Vallejo SJ, Salomon L, Doucet EL, Godeheu G, Torrens Y et al. Inhibition of monoamine oxidases desensitizes 5-HT1A autoreceptors and allows nicotine to induce a neurochemical and behavioral sensitization. J Neurosci 2009; 29: 987–997.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Tassin JP . Uncoupling between noradrenergic and serotonergic neurons as a molecular basis of stable changes in behavior induced by repeated drugs of abuse. Biochem Pharmacol 2008; 75: 85–97.

    Article  CAS  PubMed  Google Scholar 

  30. Colpaert FC, Tarayre JP, Koek W, Pauwels PJ, Bardin L, Xu XJ et al. Large-amplitude 5-HT1A receptor activation: a new mechanism of profound, central analgesia. Neuropharmacology 2002; 43: 945–958.

    Article  CAS  PubMed  Google Scholar 

  31. Lakhlani PP, MacMillan LB, Guo TZ, McCool BA, Lovinger DM, Maze M et al. Substitution of a mutant alpha2a-adrenergic receptor via ‘hit and run’ gene targeting reveals the role of this subtype in sedative, analgesic, and anesthetic-sparing responses in vivo. Proc Natl Acad Sci USA 1997; 94: 9950–9955.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Paxinos G, Franklin KBJ . The Mouse Brain in Stereotaxic Coordinates 2nd edn. Academic Press: New York, 1997.

    Google Scholar 

  33. Aghajanian GK, VanderMaelen CP . Alpha 2-adrenoceptor-mediated hyperpolarization of locus coeruleus neurons: intracellular studies in vivo. Science 1980; 215: 1394–1396.

    Article  Google Scholar 

  34. Young WS 3rd, Kuhar MJ . Noradrenergic alpha 1 and alpha 2 receptors: light microscopic autoradiographic localization. Proc Natl Acad Sci USA 1980; 77: 1696–1700.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Gozlan H, El Mestikawy S, Pichat L, Glowinski J, Hamon M . Identification of presynaptic serotonin autoreceptors using a new ligand: 3H-PAT. Nature 1983; 305: 140–142.

    Article  CAS  PubMed  Google Scholar 

  36. Haddjeri N, Lavoie N, Blier P . Electrophysiological evidence for the tonic activation of 5-HT(1A) autoreceptors in the rat dorsal raphe nucleus. Neuropsychopharmacology 2004; 29: 1800–1806.

    Article  CAS  PubMed  Google Scholar 

  37. Doze VA, Chen B-X, Maze M . Dexmedetomidine produces a hypnotic-anesthetic action in rats via activation of central, alpha sub 2-adrenoceptors. Anesthesiology 1989; 71: 75–79.

    Article  CAS  PubMed  Google Scholar 

  38. Correa-Sales C, Rabin B, Maze M . A hypnotic response to dexmedetomidine, an alpha sub 2-agonist, is mediated in the locus coeruleus in rats. Anesthesiology 1992; 76: 948–952.

    Article  CAS  PubMed  Google Scholar 

  39. Bortolozzi A, Castañé A, Semakova J, Santana N, Alvarado G, Cortés R et al. Selective siRNA-mediated suppression of 5-HT1A autoreceptors evokes strong anti-depressant-like effects. Mol Psychiatry 2012; 17: 612–623.

    Article  CAS  PubMed  Google Scholar 

  40. Mannoury la Cour C, El Mestikawy S, Hanoun N, Hamon M, Lanfumey L . Regional differences in the coupling of 5-hydroxytryptamine-1A receptors to G proteins in the rat brain. Mol Pharmacol 2006; 70: 1013–1021.

    Article  PubMed  Google Scholar 

  41. Albarrán-Juárez J, Gilsbach R, Piekorz RP, Pexa K, Beetz N, Schneider J et al. Modulation of alpha2-adrenoceptor functions by heterotrimeric Galphai protein isoforms. J Pharmacol Exp Ther 2009; 331: 35–44.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Nash JF, Brodkin J . Microdialysis studies on 3,4-methylenedioxymethamphetamine-induced dopamine release: effect of dopamine uptake inhibitors. J Pharmacol Exp Ther 1991; 259: 820–825.

    CAS  PubMed  Google Scholar 

  43. Gudelsky GA, Nash JF . Carrier-mediated release of serotonin by 3,4-methylenedioxymethamphetamine: implications for serotonin–dopamine interactions. J Neurochem 1996; 66: 243–249.

    Article  CAS  PubMed  Google Scholar 

  44. Baumann MH, Clark RD, Rothman RB . Locomotor stimulation produced by 3,4-methylenedioxymethamphetamine (MDMA) is correlated with dialysate levels of serotonin and dopamine in rat brain. Pharmacol Biochem Behav 2008; 90: 208–217.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Hysek CM, Simmler LD, Ineichen M, Grouzmann E, Hoener MC, Brenneisen R et al. The norepinephrine transporter inhibitor reboxetine reduces stimulant effects of MDMA (‘ecstasy’) in humans. Clin Pharmacol Ther 2011; 90: 246–255.

    Article  CAS  PubMed  Google Scholar 

  46. Hysek CM, Simmler LD, Nicola VG, Vischer N, Donzelli M, Krähenbühl S et al. Duloxetine inhibits effects of MDMA (‘ecstasy’) in vitro and in humans in a randomized placebo-controlled laboratory study. PLoS One 2012; 7: e36476.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Drouin C, Darracq L, Trovero F, Blanc G, Glowinski J, Cotecchia S et al. Alpha1b-adrenergic receptors control locomotor and rewarding effects of psychostimulants and opiates. J Neurosci 2002; 22: 2873–2884.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Ventura R, Cabib S, Alcaro A, Orsini C, Puglisi-Allegra S . Norepinephrine in the prefrontal cortex is critical for amphetamine-induced reward and mesoaccumbens dopamine release. J Neurosci 2003; 23: 1879–1885.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Ventura R, Alcaro A, Puglisi-Allegra S . Prefrontal cortical norepinephrine release is critical for morphine-induced reward, reinstatement and dopamine release in the nucleus accumbens. Cereb Cortex 2003; 15: 1877–1886.

    Article  Google Scholar 

  50. Olson VG, Heusner CL, Bland RJ, During MJ, Weinshenker D, Palmiter RD . Role of noradrenergic signaling by the nucleus tractus solitarius in mediating opiate reward. Science 2006; 311: 1017–1020.

    Article  CAS  PubMed  Google Scholar 

  51. Sofuoglu M, Sewell RA . Norepinephrine and stimulant addiction. Addict Biol 2009; 14: 119–129,, review.

    Article  CAS  PubMed  Google Scholar 

  52. Ungless MA, Whistler JL, Malenka RC, Bonci A . Single cocaine exposure in vivo induces long-term potentiation in dopamine neurons. Nature 2001; 411: 583–587.

    Article  CAS  PubMed  Google Scholar 

  53. Zweifel LS, Argilli E, Bonci A, Palmiter RD . Role of NMDA receptors in dopamine neurons for plasticity and addictive behaviors. Neuron 2008; 59: 486–496.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Mameli M, Halbout B, Creton C, Engblom D, Parkitna JR, Spanagel R et al. Cocaine-evoked synaptic plasticity: persistence in the VTA triggers adaptations in the NAc. Nat Neurosci 2009; 12: 1036–1041.

    Article  CAS  PubMed  Google Scholar 

  55. Segal DS, Kuczenski R . In vivo microdialysis reveals a diminished amphetamine-induced DA response corresponding to behavioral sensitization produced by repeated amphetamine pretreatment. Brain Res 1992; 571: 330–337.

    Article  CAS  PubMed  Google Scholar 

  56. Segal DS, Kuczenski R . Repeated cocaine administration induces behavioral sensitization and corresponding decreased extracellular dopamine responses in caudate and accumbens. Brain Res 1992; 577: 351–355.

    Article  CAS  PubMed  Google Scholar 

  57. Kalivas PW, Duffy P . Time course of extracellular dopamine and behavioral sensitization to cocaine. I. Dopamine axon terminals. J Neurosci 1993; 13: 266–275.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Paulson PE, Robinson TE . Amphetamine-induced time-dependent sensitization of dopamine neurotransmission in the dorsal and ventral striatum: a microdialysis study in behaving rats. Synapse 1995; 19: 56–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Ramos M, Goñi-Allo B, Aguirre N . Studies on the role of dopamine D1 receptors in the development and expression of MDMA-induced behavioral sensitization in rats. Psychopharmacology (Berl) 2004; 177: 100–110.

    Article  CAS  Google Scholar 

  60. Ramos M, Goñi-Allo B, Aguirre N . Administration of SCH 23390 into the medial prefrontal cortex blocks the expression of MDMA-induced behavioral sensitization in rats: an effect mediated by 5-HT2C receptor stimulation and not by D1 receptor blockade. Neuropsychopharmacology 2005; 30: 2180–2191.

    Article  CAS  PubMed  Google Scholar 

  61. White FJ, Joshi A, Koeltzow TE, Hu XT . Dopamine receptor antagonists fail to prevent induction of cocaine sensitization. Neuropsychopharmacology 1998; 18: 26–40.

    Article  CAS  PubMed  Google Scholar 

  62. Granado N, O'Shea E, Bove J, Vila M, Colado MI, Moratalla R . Persistent MDMA-induced dopaminergic neurotoxicity in the striatum and substantia nigra of mice. J Neurochem 2008; 107: 1102–1112.

    CAS  PubMed  Google Scholar 

  63. O'Callaghan JP, Miller DB . Neurotoxicity profiles of substituted amphetamines in the C57BL/6J mouse. J Pharmacol Exp Ther 1994; 270: 741–751.

    CAS  PubMed  Google Scholar 

  64. Logan BJ, Laverty R, Sanderson WD, Yee YB . Differences between rats and mice in MDMA (methylenedioxymethylamphetamine) neurotoxicity. Eur J Pharmacol 1988; 152: 227–234.

    Article  CAS  PubMed  Google Scholar 

  65. Stone DM, Hanson GR, Gibb JW . Differences in the central serotonergic effects of methylenedioxymethamphetamine (MDMA) in mice and rats. Neuropharmacology 1987; 26: 1657–1661.

    Article  CAS  PubMed  Google Scholar 

  66. Nestler EJ, Terwilliger RZ, Walker JR, Sevarino KA, Duman RS . Chronic cocaine treatment decreases levels of the G protein subunits Gi alpha and Go alpha in discrete regions of rat brain. J Neurochem 1990; 55: 1079–1082.

    Article  CAS  PubMed  Google Scholar 

  67. Giguère PM, Laroche G, Oestreich EA, Duncan JA, Siderovski DP . Regulation of the subcellular localization of the G-protein subunit regulator GPSM3 through direct association with 14-3-3 protein. J Biol Chem 2012; 287: 31270–31279.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Baraban JM, Aghajanian GK . Suppression of firing activity of 5-HT neurons in the dorsal raphe by alpha-adrenoceptor antagonists. Neuropharmacology 1980; 19: 355–363.

    Article  CAS  PubMed  Google Scholar 

  69. Bortolozzi A, Artigas F . Control of 5-hydroxytryptamine release in the dorsal raphe nucleus by the noradrenergic system in rat brain. Role of alpha-adrenoceptors. Neuropsychopharmacology 2003; 28: 421–434.

    Article  CAS  PubMed  Google Scholar 

  70. Gorea E, Adrien J . Serotonergic regulation of noradrenergic coerulean neurons: electrophysiological evidence for the involvement of 5-HT2 receptors. Eur J Pharmacol 1988; 154: 285–291.

    Article  CAS  PubMed  Google Scholar 

  71. Szabo ST, Blier P . Functional and pharmacological characterization of the modulatory role of serotonin on the firing activity of locus coeruleus norepinephrine neurons. Brain Res 2001; 922: 9–20.

    Article  CAS  PubMed  Google Scholar 

  72. Jedema HP, Grace AA . Chronic exposure to cold stress alters electrophysiological properties of locus coeruleus neurons recorded in vitro. Neuropsychopharmacology 2003; 28: 63–72.

    Article  PubMed  Google Scholar 

  73. Jedema HP, Gold SJ, Gonzalez-Burgos G, Sved AF, Tobe BJ, Wensel T et al. Chronic cold exposure increases RGS7 expression and decreases alpha(2)-autoreceptor-mediated inhibition of noradrenergic locus coeruleus neurons. Eur J Neurosci 2008; 27: 2433–2443.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Lanfumey L, Pardon MC, Laaris N, Joubert C, Hanoun N, Hamon M et al. 5-HT1A autoreceptor desensitization by chronic ultramild stress in mice. NeuroReport 1999; 10: 3369–3374.

    Article  CAS  PubMed  Google Scholar 

  75. Froger N, Palazzo E, Boni C, Hanoun N, Saurini F, Joubert C et al. Neurochemical and behavioral alterations in glucocorticoid receptor-impaired transgenic mice after chronic mild stress. J Neurosci 2004; 24: 2787–2796.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Antelman SM, Eichler AJ, Black CA, Kocan D . Interchangeability of stress and amphetamine in sensitization. Science 1980; 207: 329–331.

    Article  CAS  PubMed  Google Scholar 

  77. Deroche V, Marinelli M, Maccari S, Le Moal M, Simon H, Piazza PV . Stress-induced sensitization and glucocorticoids. I. Sensitization of dopamine-dependent locomotor effects of amphetamine and morphine depends on stress-induced corticosterone secretion. J Neurosci 1995; 15: 7181–7188.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Rougé-Pont F, Marinelli M, Le Moal M, Simon H, Piazza P . Stress-induced sensitization and glucocorticoids. II. Sensitization of the increase in extracellular dopamine induced by cocaine depends on stress-induced corticosterone secretion. J Neurosci 1995; 15: 7189–7195.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Abercrombie ED, Jacobs BL . Single-unit response of noradrenergic neurons in the locus coeruleus of freely moving cats. II. Adaptation to chronically presented stressful stimuli. J Neurosci 1987a; 7: 2844–2848.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Abercrombie ED, Jacobs BL . Single-unit response of noradrenergic neurons in the locus coeruleus of freely moving cats. I. Acutely presented stressful and nonstressful stimuli. J Neurosci 1987b; 7: 2837–2843.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Price ML, Curtis AL, Kirby LG, Valentino RJ, Lucki I . Effects of corticotropin-releasing factor on brain serotonergic activity. Neuropsychopharmacology 1998; 18: 492–502.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by Université Pierre et Marie Curie (UPMC), Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique (CNRS) and Institut National de la Santé et de la Recherche Médicale (Inserm). We thank Drs Francis Colpaert (†) and Pierre Sokollof (Laboratoires Pierre Fabre, Castres, France) for kindly providing us F13640. We also thank Dr Marie-Pascale Martres and Caroline Chevarin for her help with radiolabeling experiments; Dr Marie Picot and Nicolas ‘boubou’ Bouveyron for their precious advices on western blot experiments; and Carole Jacq for her help with behavioral experiments. CL would like to thank Vanessa Houades for her support. This work is dedicated to the memory of Iderlinda Deus de Sousa.

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  1. Laboratoire de Physiopathologie des Maladies du Système Nerveux Central, CNRS UMR 7224,, Paris, France

    C Lanteri, E L Doucet, G Godeheu, A-C Bobadilla & J-P Tassin

  2. Inserm UMR S952, Paris, France

    C Lanteri, E L Doucet, G Godeheu, A-C Bobadilla & J-P Tassin

  3. Université Pierre et Marie Curie, 7–9 quai Saint Bernard, 75252, Paris, France

    C Lanteri, E L Doucet, G Godeheu, A-C Bobadilla & J-P Tassin

  4. Inserm U1016, Institut Cochin, Paris, France

    S J Hernández Vallejo

  5. CNRS UMR 7148, Collège de France, Paris, France

    L Salomon

  6. Inserm UMR S894, Centre de Psychiatrie et de Neurosciences, Paris, France

    L Lanfumey

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  1. C Lanteri
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CL and JPT designed the study. CL, ELD, SJHV, GG, ACB and LS performed research. CL, ELD, SJHV, ACB, LL and JPT analyzed the data. CL wrote the manuscript.

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Lanteri, C., Doucet, E., Hernández Vallejo, S. et al. Repeated exposure to MDMA triggers long-term plasticity of noradrenergic and serotonergic neurons. Mol Psychiatry 19, 823–833 (2014). https://doi.org/10.1038/mp.2013.97

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