Skip to main content
SpringerLink
Log in

Inhibition of serotonin transporters disrupts the enhancement of fear memory extinction by 3,4-methylenedioxymethamphetamine (MDMA)

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

3,4-Methylenedioxymethamphetamine (MDMA) persistently improves symptoms of post-traumatic stress disorder (PTSD) when combined with psychotherapy. Studies in rodents suggest that these effects can be attributed to enhancement of fear memory extinction. Therefore, MDMA may improve the effects of exposure-based therapy for PTSD, particularly in treatment-resistant patients. However, given MDMA’s broad pharmacological profile, further investigation is warranted before moving to a complex clinical population.

Objectives

We aimed to inform clinical research by providing a translational model of MDMA’s effect, and elucidating monoaminergic mechanisms through which MDMA enhances fear extinction.

Methods

We explored the importance of monoamine transporters targeted by MDMA to fear memory extinction, as measured by reductions in conditioned freezing and fear-potentiated startle (FPS) in mice. Mice were treated with selective inhibitors of individual monoamine transporters prior to combined MDMA treatment and fear extinction training.

Results

MDMA enhanced the lasting extinction of FPS. Acute and chronic treatment with a 5-HT transporter (5-HTT) inhibitor blocked MDMA’s effect on fear memory extinction. Acute inhibition of dopamine (DA) and norepinephrine (NE) transporters had no effect. 5-HT release alone did not enhance extinction. Blockade of MDMA’s effect by 5-HTT inhibition also downregulated 5-HT2A-mediated behavior, and 5-HT2A antagonism disrupted MDMA’s effect on extinction.

Conclusions

We validate enhancement of fear memory extinction by MDMA in a translational behavioral model, and reveal the importance of 5-HTT and 5-HT2A receptors to this effect. These observations support future clinical research of MDMA as an adjunct to exposure therapy, and provide important pharmacological considerations for clinical use in a population frequently treated with 5-HTT inhibitors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Abraham AD, Cunningham CL, Lattal KM (2012) Methylphenidate enhances extinction of contextual fear. Learn Mem (Cold Spring Harbor, NY) 19:67–72

    Article  CAS  Google Scholar 

  • Asan E, Steinke M, Lesch KP (2013) Serotonergic innervation of the amygdala: targets, receptors, and implications for stress and anxiety. Histochem Cell Biol 139:785–813

    Article  CAS  PubMed  Google Scholar 

  • Balu DT, Turner JR, Brookshire BR, Hill-Smith TE, Blendy JA, Lucki I (2013) Brain monoamines and antidepressant-like responses in MRL/MpJ versus C57BL/6J mice. Neuropharmacology 67:503–510

    Article  CAS  PubMed  Google Scholar 

  • Battaglia G, Brooks BP, Kulsakdinun C, De Souza EB (1988) Pharmacologic profile of MDMA (3,4-methylenedioxymethamphetamine) at various brain recognition sites. Eur J Pharmacol 149:159–163

    Article  CAS  PubMed  Google Scholar 

  • Benmansour S, Cecchi M, Morilak DA, Gerhardt GA, Javors MA, Gould GG, Frazer A (1999) Effects of chronic antidepressant treatments on serotonin transporter function, density, and mRNA level. J Neurosci 19:10494–10501

    CAS  PubMed  Google Scholar 

  • Benmansour S, Owens WA, Cecchi M, Morilak DA, Frazer A (2002) Serotonin clearance in vivo is altered to a greater extent by antidepressant-induced downregulation of the serotonin transporter than by acute blockade of this transporter. J Neurosci 22:6766–6772

    CAS  PubMed  Google Scholar 

  • Berg KA, Stout BD, Maayani S, Clarke WP (2001) Differences in rapid desensitization of 5-hydroxytryptamine2A and 5-hydroxytryptamine2C receptor-mediated phospholipase C activation. J Pharmacol Exp Ther 299:593–602

    CAS  PubMed  Google Scholar 

  • Bershad AK, Weafer JJ, Kirkpatrick MG, Wardle MC, Miller MA, de Wit H (2016) Oxytocin receptor gene variation predicts subjective responses to MDMA. Soc Neurosci 11:592–599

    Article  PubMed  PubMed Central  Google Scholar 

  • Bocchio M, Fucsina G, Oikonomidis L, McHugh SB, Bannerman DM, Sharp T, Capogna M (2015) Increased serotonin transporter expression reduces fear and recruitment of parvalbumin interneurons of the amygdala. Neuropsychopharmacology 40:3015–3026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Borowski TB, Kokkinidis L (1998) The effects of cocaine, amphetamine, and the dopamine D1 receptor agonist SKF 38393 on fear extinction as measured with potentiated startle: implications for psychomotor stimulant psychosis. Behav Neurosci 112:952–965

    Article  CAS  PubMed  Google Scholar 

  • Boyer PA, Skolnick P, Fossom LH (1998) Chronic administration of imipramine and citalopram alters the expression of NMDA receptor subunit mRNAs in mouse brain. A quantitative in situ hybridization study Journal of molecular neuroscience : MN 10:219–233

    Article  CAS  PubMed  Google Scholar 

  • Briscione MA, Jovanovic T, Norrholm SD (2014) Conditioned fear associated phenotypes as robust, translational indices of trauma-, stressor-, and anxiety-related behaviors. Frontiers Psychiatry 5:88

    Article  Google Scholar 

  • Burghardt NS, Bauer EP (2013) Acute and chronic effects of selective serotonin reuptake inhibitor treatment on fear conditioning: implications for underlying fear circuits. Neuroscience 247:253–272

    Article  CAS  PubMed  Google Scholar 

  • Burghardt NS, Sigurdsson T, Gorman JM, McEwen BS, LeDoux JE (2013) Chronic antidepressant treatment impairs the acquisition of fear extinction. Biol Psychiatry 73:1078–1086

    Article  CAS  PubMed  Google Scholar 

  • Carmack SA, Wood SC, Anagnostaras SG (2010) Amphetamine and extinction of cued fear. Neurosci Lett 468:18–22

    Article  CAS  PubMed  Google Scholar 

  • Carroll FI, Howard JL, Howell LL, Fox BS, Kuhar MJ (2006) Development of the dopamine transporter selective RTI-336 as a pharmacotherapy for cocaine abuse. AAPS J 8:E196–E203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Catlow BJ, Song S, Paredes DA, Kirstein CL, Sanchez-Ramos J (2013) Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning. Exp Brain Res 228:481–491

    Article  CAS  PubMed  Google Scholar 

  • Chaudhury D, Colwell CS (2002) Circadian modulation of learning and memory in fear-conditioned mice. Behav Brain Res 133:95–108

    Article  PubMed  Google Scholar 

  • Crespi D, Mennini T, Gobbi M (1997) Carrier-dependent and Ca(2+)-dependent 5-HT and dopamine release induced by (+)-amphetamine, 3,4-methylendioxymethamphetamine, p-chloroamphetamine and (+)-fenfluramine. Br J Pharmacol 121:1735–1743

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Daldrup T, Remmes J, Lesting J, Gaburro S, Fendt M, Meuth P, Kloke V, Pape HC, Seidenbecher T (2015) Expression of freezing and fear-potentiated startle during sustained fear in mice. Genes Brain Behav 14:281–291

    Article  CAS  PubMed  Google Scholar 

  • Davis M (2006) Neural systems involved in fear and anxiety measured with fear-potentiated startle. Am Psychol 61:741–756

    Article  PubMed  Google Scholar 

  • de Kleine RA, Rothbaum BO, van Minnen A (2013) Pharmacological enhancement of exposure-based treatment in PTSD: a qualitative review. Eur J Psychotraumatol 4:21626

    Article  Google Scholar 

  • de Paula BB, Leite-Panissi CR (2016) Distinct effect of 5-HT1A and 5-HT2A receptors in the medial nucleus of the amygdala on tonic immobility behavior. Brain Res 1643:152–158

    Article  PubMed  Google Scholar 

  • Dougherty JP, Aloyo VJ (2011) Pharmacological and behavioral characterization of the 5-HT2A receptor in C57BL/6N mice. Psychopharmacology 215:581–593

    Article  CAS  PubMed  Google Scholar 

  • Fitzgerald JL, Reid JJ (1990) Effects of methylenedioxymethamphetamine on the release of monoamines from rat brain slices. Eur J Pharmacol 191:217–220

    Article  CAS  PubMed  Google Scholar 

  • Fredricson Overo K (1982) Kinetics of citalopram in test animals; drug exposure in safety studies. Prog Neuro-Psychopharmacol Biol Psychiatry 6:297–309

    Article  CAS  Google Scholar 

  • Green AR, Mechan AO, Elliott JM, O'Shea E, Colado MI (2003) The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”). Pharmacol Rev 55:463–508

    Article  CAS  PubMed  Google Scholar 

  • Greer G, Tolbert R (1986) Subjective reports of the effects of MDMA in a clinical setting. J Psychoactive Drugs 18:319–327

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Gunduz-Cinar O, Flynn S, Brockway E, Kaugars K, Baldi R, Ramikie TS, Cinar R, Kunos G, Patel S, Holmes A (2016) Fluoxetine facilitates fear extinction through amygdala endocannabinoids. Neuropsychopharmacology 41:1598–1609

    Article  CAS  PubMed  Google Scholar 

  • Hasler F, Studerus E, Lindner K, Ludewig S, Vollenweider F (2009) Investigation of serotonin-1A receptor function in the human psychopharmacology of MDMA. J Psychopharmacol 23:923–935

    Article  CAS  PubMed  Google Scholar 

  • Hekmatpanah CR, Peroutka SJ (1990) 5-hydroxytryptamine uptake blockers attenuate the 5-hydroxytryptamine-releasing effect of 3,4-methylenedioxymethamphetamine and related agents. Eur J Pharmacol 177:95–98

    Article  CAS  PubMed  Google Scholar 

  • Hughes CR, Tran T, Keele NB (2012) 5-HT2A receptor activation normalizes exaggerated fear behavior in p-chlorophenylalanine (PCPA)-treated rats. J Behav Brain Sci 2:454–462

    Article  Google Scholar 

  • Hunt GE, McGregor IS, Cornish JL, Callaghan PD (2011) MDMA-induced c-Fos expression in oxytocin-containing neurons is blocked by pretreatment with the 5-HT-1A receptor antagonist WAY 100635. Brain Res Bull 86:65–73

    Article  CAS  PubMed  Google Scholar 

  • Hysek CM, Simmler LD, Ineichen M, Grouzmann E, Hoener MC, Brenneisen R, Huwyler J, Liechti ME (2011) The norepinephrine transporter inhibitor reboxetine reduces stimulant effects of MDMA (“ecstasy”) in humans. Clin Pharmacol Ther 90:246–255

    Article  CAS  PubMed  Google Scholar 

  • Hysek CM, Simmler LD, Nicola VG, Vischer N, Donzelli M, Krahenbuhl S, Grouzmann E, Huwyler J, Hoener MC, Liechti ME (2012) Duloxetine inhibits effects of MDMA (“ecstasy”) in vitro and in humans in a randomized placebo-controlled laboratory study. PLoS One 7:e36476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hysek CM, Vollenweider FX, Liechti ME (2010) Effects of a beta-blocker on the cardiovascular response to MDMA (ecstasy). Emerg Med J: EMJ 27:586–589

    Article  CAS  PubMed  Google Scholar 

  • Jennings KA, Sheward WJ, Harmar AJ, Sharp T (2008) Evidence that genetic variation in 5-HT transporter expression is linked to changes in 5-HT2A receptor function. Neuropharmacology 54:776–783

    Article  CAS  PubMed  Google Scholar 

  • Karlsson L, Carlsson B, Hiemke C, Ahlner J, Bengtsson F, Schmitt U, Kugelberg FC (2013) Altered brain concentrations of citalopram and escitalopram in P-glycoprotein deficient mice after acute and chronic treatment. Eur Neuropsychopharmacology: J Eur Coll Neuropsychopharmacology 23:1636–1644

    Article  CAS  Google Scholar 

  • Karpova NN, Pickenhagen A, Lindholm J, Tiraboschi E, Kulesskaya N, Agustsdottir A, Antila H, Popova D, Akamine Y, Bahi A, Sullivan R, Hen R, Drew LJ, Castren E (2011) Fear erasure in mice requires synergy between antidepressant drugs and extinction training. Science 334:1731–1734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kehne JH, Baron BM, Carr AA, Chaney SF, Elands J, Feldman DJ, Frank RA, van Giersbergen PL, McCloskey TC, Johnson MP, McCarty DR, Poirot M, Senyah Y, Siegel BW, Widmaier C (1996) Preclinical characterization of the potential of the putative atypical antipsychotic MDL 100,907 as a potent 5-HT2A antagonist with a favorable CNS safety profile. J Pharmacol Exp Ther 277:968–981

    CAS  PubMed  Google Scholar 

  • Kimmel HL, Negus SS, Wilcox KM, Ewing SB, Stehouwer J, Goodman MM, Votaw JR, Mello NK, Carroll FI, Howell LL (2008) Relationship between rate of drug uptake in brain and behavioral pharmacology of monoamine transporter inhibitors in rhesus monkeys. Pharmacol Biochem Behav 90:453–462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koen N, Stein DJ (2011) Pharmacotherapy of anxiety disorders: a critical review. Dialogues Clin Neurosci 13:423–437

    PubMed  PubMed Central  Google Scholar 

  • Kreilgaard M, Smith DG, Brennum LT, Sanchez C (2008) Prediction of clinical response based on pharmacokinetic/pharmacodynamic models of 5-hydroxytryptamine reuptake inhibitors in mice. Br J Pharmacol 155:276–284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kuczenski R, Segal DS (1997) Effects of methylphenidate on extracellular dopamine, serotonin, and norepinephrine: comparison with amphetamine. J Neurochem 68:2032–2037

    Article  CAS  PubMed  Google Scholar 

  • Lanteri C, Doucet EL, Hernandez Vallejo SJ, Godeheu G, Bobadilla AC, Salomon L, Lanfumey L, Tassin JP (2014) Repeated exposure to MDMA triggers long-term plasticity of noradrenergic and serotonergic neurons. Mol Psychiatry 19:823–833

    Article  CAS  PubMed  Google Scholar 

  • Liechti ME, Saur MR, Gamma A, Hell D, Vollenweider FX (2000) Psychological and physiological effects of MDMA (“ecstasy”) after pretreatment with the 5-HT(2) antagonist ketanserin in healthy humans. Neuropsychopharmacology 23:396–404

    Article  CAS  PubMed  Google Scholar 

  • Liechti ME, Vollenweider FX (2000a) Acute psychological and physiological effects of MDMA (“ecstasy”) after haloperidol pretreatment in healthy humans. Eur Neuropsychopharmacology: J Eur Coll Neuropsychopharmacol 10:289–295

    Article  CAS  Google Scholar 

  • Liechti ME, Vollenweider FX (2000b) The serotonin uptake inhibitor citalopram reduces acute cardiovascular and vegetative effects of 3,4-methylenedioxymethamphetamine (‘Ecstasy’) in healthy volunteers. J Psychopharmacol (Oxford, England) 14:269–274

    Article  CAS  Google Scholar 

  • McDonald AJ, Mascagni F (2007) Neuronal localization of 5-HT type 2A receptor immunoreactivity in the rat basolateral amygdala. Neuroscience 146:306–320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meyer JH, Kapur S, Eisfeld B, Brown GM, Houle S, DaSilva J, Wilson AA, Rafi-Tari S, Mayberg HS, Kennedy SH (2001) The effect of paroxetine on 5-HT(2A) receptors in depression: an [(18)F]setoperone PET imaging study. Am J Psychiatry 158:78–85

    Article  CAS  PubMed  Google Scholar 

  • Mithoefer MC, Wagner MT, Mithoefer AT, Jerome L, Doblin R (2011) The safety and efficacy of {+/−}3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. J Psychopharmacol (Oxford, England) 25:439–452

    Article  CAS  Google Scholar 

  • Mithoefer MC, Wagner MT, Mithoefer AT, Jerome L, Martin SF, Yazar-Klosinski B, Michel Y, Brewerton TD, Doblin R (2013) Durability of improvement in post-traumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study. J Psychopharmacol (Oxford, England) 27:28–39

    Article  CAS  Google Scholar 

  • Morley KC, Arnold JC, McGregor IS (2005) Serotonin (1A) receptor involvement in acute 3,4-methylenedioxymethamphetamine (MDMA) facilitation of social interaction in the rat. Prog Neuro-Psychopharmacol Biol Psychiatry 29:648–657

    Article  CAS  Google Scholar 

  • Mueller D, Bravo-Rivera C, Quirk GJ (2010) Infralimbic D2 receptors are necessary for fear extinction and extinction-related tone responses. Biol Psychiatry 68:1055–1060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mueller D, Cahill SP (2010) Noradrenergic modulation of extinction learning and exposure therapy. Behav Brain Res 208:1–11

    Article  CAS  PubMed  Google Scholar 

  • Mueller D, Porter JT, Quirk GJ (2008) Noradrenergic signaling in infralimbic cortex increases cell excitability and strengthens memory for fear extinction. J Neurosci 28:369–375

    Article  CAS  PubMed  Google Scholar 

  • Murchison CF, Zhang XY, Zhang WP, Ouyang M, Lee A, Thomas SA (2004) A distinct role for norepinephrine in memory retrieval. Cell 117:131–143

    Article  CAS  PubMed  Google Scholar 

  • Murnane KS, Fantegrossi WE, Godfrey JR, Banks ML, Howell LL (2010) Endocrine and neurochemical effects of 3,4-methylenedioxymethamphetamine and its stereoisomers in rhesus monkeys. J Pharmacol Exp Ther 334:642–650

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Murnane KS, Kimmel HL, Rice KC, Howell LL (2012) The neuropharmacology of prolactin secretion elicited by 3,4-methylenedioxymethamphetamine (“ecstasy”): a concurrent microdialysis and plasma analysis study. Horm Behav 61:181–190

    Article  CAS  PubMed  Google Scholar 

  • Myers KM, Davis M (2002) Behavioral and neural analysis of extinction. Neuron 36:567–584

    Article  CAS  PubMed  Google Scholar 

  • Myers KM, Davis M (2007) Mechanisms of fear extinction. Mol Psychiatry 12:120–150

    Article  CAS  PubMed  Google Scholar 

  • Norrholm SD, Jovanovic T, Vervliet B, Myers KM, Davis M, Rothbaum BO, Duncan EJ (2006) Conditioned fear extinction and reinstatement in a human fear-potentiated startle paradigm. Learn Mem (Cold Spring Harbor, NY) 13:681–685

    Article  Google Scholar 

  • Rauch SA, King AP, Abelson J, Tuerk PW, Smith E, Rothbaum BO, Clifton E, Defever A, Liberzon I (2015) Biological and symptom changes in posttraumatic stress disorder treatment: a randomized clinical trial. Depress anxiety 32:204–212

    Article  PubMed  Google Scholar 

  • Risbrough VB, Brodkin JD, Geyer MA (2003) GABA-A and 5-HT1A receptor agonists block expression of fear-potentiated startle in mice. Neuropsychopharmacology 28:654–663

    Article  CAS  PubMed  Google Scholar 

  • Rothbaum BO, Davis M (2003) Applying learning principles to the treatment of post-trauma reactions. Ann N Y Acad Sci 1008:112–121

    Article  PubMed  Google Scholar 

  • Rothbaum BO, Schwartz AC (2002) Exposure therapy for posttraumatic stress disorder. Am J Psychother 56:59–75

    PubMed  Google Scholar 

  • Sanchez C, Hyttel J (1999) Comparison of the effects of antidepressants and their metabolites on reuptake of biogenic amines and on receptor binding. Cell Mol Neurobiol 19:467–489

    Article  CAS  PubMed  Google Scholar 

  • Sawyer EK, Mun J, Nye JA, Kimmel HL, Voll RJ, Stehouwer JS, Rice KC, Goodman MM, Howell LL (2012) Neurobiological changes mediating the effects of chronic fluoxetine on cocaine use. Neuropsychopharmacology 37:1816–1824

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singewald N, Schmuckermair C, Whittle N, Holmes A, Ressler KJ (2015) Pharmacology of cognitive enhancers for exposure-based therapy of fear, anxiety and trauma-related disorders. Pharmacol Ther 149:150–190

    Article  CAS  PubMed  Google Scholar 

  • Slipczuk L, Tomaiuolo M, Garagoli F, Weisstaub N, Katche C, Bekinschtein P, Medina JH (2013) Attenuating the persistence of fear memory storage using a single dose of antidepressant. Mol Psychiatry 18:7–8

    Article  CAS  PubMed  Google Scholar 

  • Smith KS, Meloni EG, Myers KM, Van't Veer A, Carlezon WA Jr, Rudolph U (2011) Reduction of fear-potentiated startle by benzodiazepines in C57BL/6J mice. Psychopharmacology 213:697–706

    Article  CAS  PubMed  Google Scholar 

  • Strolin Benedetti M, Frigerio E, Tocchetti P, Brianceschi G, Castelli MG, Pellizzoni C, Dostert P (1995) Stereoselective and species-dependent kinetics of reboxetine in mouse and rat. Chirality 7:285–289

    Article  CAS  PubMed  Google Scholar 

  • van Wel JH, Kuypers KP, Theunissen EL, Bosker WM, Bakker K, Ramaekers JG (2012) Effects of acute MDMA intoxication on mood and impulsivity: role of the 5-HT2 and 5-HT1 receptors. PLoS One 7:e40187

    Article  PubMed  PubMed Central  Google Scholar 

  • Vouret-Craviari V, Auberger P, Pouyssegur J, Van Obberghen-Schilling E (1995) Distinct mechanisms regulate 5-HT2 and thrombin receptor desensitization. J Biol Chem 270:4813–4821

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto BK, Nash JF, Gudelsky GA (1995) Modulation of methylenedioxymethamphetamine-induced striatal dopamine release by the interaction between serotonin and gamma-aminobutyric acid in the substantia nigra. J Pharmacol Exp Ther 273:1063–1070

    CAS  PubMed  Google Scholar 

  • Young MB, Andero R, Ressler KJ, Howell LL (2015) 3,4-Methylenedioxymethamphetamine facilitates fear extinction learning. Transl Psychiatry 5:e634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang G, Asgeirsdottir HN, Cohen SJ, Munchow AH, Barrera MP, Stackman RW Jr (2013) Stimulation of serotonin 2A receptors facilitates consolidation and extinction of fear memory in C57BL/6J mice. Neuropharmacology 64:403–413

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors appreciate the Abraham J. & Phyllis Katz Foundation for support of this research. We thank the animal care and veterinary staff at the Yerkes National Primate Research Center (YNPRC) for maintaining the health and well-being of our research subjects, whom we thank greatly for their contribution. M.B.Y. thanks Dr. Brian Dias for use of valuable behavioral equipment. M.B.Y. also thanks Daniel Curry and Karly Hampshire for assistance with behavioral experiments. The YNPRC is fully accredited by the American Association for Accreditation for Laboratory Animal Care. This research complied with all laws of the USA.

Author information

Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 954 Gatewood Rd NE #2101, Atlanta, GA, 30329, USA

    Matthew B. Young, Seth D. Norrholm, Tanja Jovanovic, Sheila A.M. Rauch, Collin M. Reiff, Boadie W. Dunlop, Barbara O. Rothbaum & Leonard L. Howell

  2. Atlanta VA Medical Center, Mental Health Service Line, Decatur, GA, USA

    Seth D. Norrholm, Tanja Jovanovic & Sheila A.M. Rauch

  3. Emory University, Atlanta, GA, USA

    Lara M. Khoury

Authors
  1. Matthew B. Young
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Seth D. Norrholm
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lara M. Khoury
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tanja Jovanovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sheila A.M. Rauch
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Collin M. Reiff
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Boadie W. Dunlop
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Barbara O. Rothbaum
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Leonard L. Howell
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Leonard L. Howell.

Ethics declarations

Studies were in accordance with National Institutes of Health guidelines, and all procedures were approved by the Institutional Animal Care and Use Committee at Emory University.

Funding

M.B.Y. became employed by Shire Pharmaceuticals (Lexington, MA, USA) after completion of the studies described herein. M.B.Y. was supported by a NIH/NIGMS IRACDA grant K21 GM000680 awarded to Emory University. L.L.H. was supported by NIH/NIDA K05 DA031246. B.O.R. has funding from Wounded Warrior Project, Department of Defense Clinical Trial Grant No. W81XWH-10-1-1045, “Enhancing Exposure Therapy for PTSD: Virtual Reality and Imaginal Exposure with a Cognitive Enhancer,” National Institute of Mental Health Grant No. 1R01MH094757-01, “Prospective Determination of Psychobiological Risk Factors for Posttraumatic Stress,” Brain and Behavior Research Foundation (NARSAD) Distinguished Investigator Grant, “Optimal Dose of early intervention to prevent PTSD,” and McCormick Foundation “Brave Heart: MLB’s Welcome Back Veterans SouthEast Initiative.” Dr. Rothbaum receives royalties from Oxford University Press, Guilford, APPI, and Emory University and received one advisory board payment from Genentech. B.W.D. has received research support from Assurex, Axsome, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, NIMH, Otsuka, Pfizer, and Takeda. He has served as a consultant to Pfizer and Medavante.

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Young, M.B., Norrholm, S.D., Khoury, L.M. et al. Inhibition of serotonin transporters disrupts the enhancement of fear memory extinction by 3,4-methylenedioxymethamphetamine (MDMA). Psychopharmacology 234, 2883–2895 (2017). https://doi.org/10.1007/s00213-017-4684-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-017-4684-8

Keywords

Search

Navigation