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Non-medical and illicit use of psychoactive drugs pp 17–32Cite as

Contribution of Impulsivity and Serotonin Receptor Neuroadaptations to the Development of an MDMA (‘Ecstasy’) Substance Use Disorder

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Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 34))

Abstract

As is the case with other drugs of abuse, a proportion of ecstasy users develop symptoms consistent with a substance use disorder (SUD). In this paper, we propose that the pharmacology of MDMA, the primary psychoactive component of ecstasy tablets, changes markedly with repeated exposure and that neuroadaptations in dopamine and serotonin brain systems underlie the shift from MDMA use to MDMA misuse in susceptible subjects. Data from both the human and laboratory animal literature are synthesized to support the idea that (1) MDMA becomes a less efficacious serotonin releaser and a more efficacious dopamine releaser with the development of behaviour consistent with an SUD and (2) that upregulated serotonin receptor mechanisms contribute to the development of the MDMA SUD via dysregulated inhibitory control associated with the trait of impulsivity.

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References

  • Alex KD, Pehek EA (2007) Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission. Pharmacol Ther 113(2):296–320

    Article  CAS  PubMed  Google Scholar 

  • Anastasio NC et al (2011) The serotonin (5-Ht) 5-Ht2a receptor: association with inherent and cocaine-evoked behavioral disinhibition in rats. Behav Pharmacol 22(3):248

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Anastasio NC et al (2015) Serotonin (5-HT) 5-HT2A receptor (5-HT2AR): 5-HT2CR imbalance in medial prefrontal cortex associates with motor impulsivity. ACS Chem Neurosci 6(7):1248–1258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aznar S, Klein AB (2013) Regulating prefrontal cortex activation: an emerging role for the 5-HT(2)A serotonin receptor in the modulation of emotion-based actions? Mol Neurobiol 48(3):841–853

    Article  CAS  PubMed  Google Scholar 

  • Ball KT et al (2009) Sensitizing regimens of (+/−)3, 4-methylenedioxymethamphetamine (ecstasy) elicit enduring and differential structural alterations in the brain motive circuit of the rat. Neuroscience 160(2):264–274

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ball KT et al (2010) Electrophysiological and structural alterations in striatum associated with behavioral sensitization to (+/−)3,4-methylenedioxymethamphetamine (ecstasy) in rats: role of drug context. Neuroscience 171(3):794–811

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ball KT et al (2011) Behavioral sensitization to 3,4-methylenedioxymethamphetamine is long-lasting and modulated by the context of drug administration. Behav Pharmacol 22(8):847–850

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bankson MG, Cunningham KA (2002) Pharmacological studies of the acute effects of (+)-3,4-methylenedioxymethamphetamine on locomotor activity: role of 5-HT(1B/1D) and 5-HT(2) receptors. Neuropsychopharmacology 26(1):40–52

    Article  CAS  PubMed  Google Scholar 

  • Baumann MH et al (2008) Tolerance to 3,4-methylenedioxymethamphetamine in rats exposed to single high-dose binges. Neuroscience 152(3):773–784

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Beckwith S, Czachowski CL (2014) Increased delay discounting tracks with a high ethanol-seeking phenotype and subsequent ethanol seeking but not consumption. Alcohol Clin Exp Res 38(10):2607–2614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Belin D et al (2008) High impulsivity predicts the switch to compulsive cocaine-taking. Science 320(5881):1352–1355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Benningfield MM, Cowan RL (2013) Brain serotonin function in MDMA (ecstasy) users: evidence for persisting neurotoxicity. Neuropsychopharmacology 38(1):253–255

    Article  PubMed  Google Scholar 

  • Biezonski DK, Meyer JS (2011) The nature of 3,4-methylenedioxymethamphetamine (MDMA)-induced serotonergic dysfunction: evidence for and against the neurodegeneration hypothesis. Curr Neuropharmacol 9(1):84–90

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bird J, Schenk S (2013) Contribution of impulsivity and novelty-seeking to the acquisition and maintenance of MDMA self-administration. Addict Biol 18(4):654–664

    Article  CAS  PubMed  Google Scholar 

  • Blokland A (1998) Reaction time responding in rats. Neurosci Biobehav Rev 22(6):847–864

    Article  CAS  PubMed  Google Scholar 

  • Blokland A, Sik A, Lieben C (2005) Evaluation of DOI, 8-OH-DPAT, eticlopride and amphetamine on impulsive responding in a reaction time task in rats. Behav Pharmacol 16(2):93–100

    Article  CAS  PubMed  Google Scholar 

  • Bosch OG et al (2013) Verbal memory deficits are correlated with prefrontal hypometabolism in (18)FDG PET of recreational MDMA users. PLoS ONE 8(4):e61234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bradbury S, Gittings D, Schenk S (2012) Repeated exposure to MDMA and amphetamine: sensitization, cross-sensitization, and response to dopamine D(1)- and D(2)-like agonists. Psychopharmacology 223(4):389–399

    Article  CAS  PubMed  Google Scholar 

  • Bradbury S et al (2014) Acquisition of MDMA self-administration: pharmacokinetic factors and MDMA-induced serotonin release. Addict Biol 19(5):874–884

    Article  CAS  PubMed  Google Scholar 

  • Brennan KA et al (2009) Effect of D1-like and D2-like receptor antagonists on methamphetamine and 3,4-methylenedioxymethamphetamine self-administration in rats. Behav Pharmacol 20(8):688–694

    Article  CAS  PubMed  Google Scholar 

  • Bubar MJ et al (2004) Effects of dopamine D1- or D2-like receptor antagonists on the hypermotive and discriminative stimulus effects of (+)-MDMA. Psychopharmacology 173(3–4):326–336

    Article  CAS  PubMed  Google Scholar 

  • Cadoni C et al (2005) Effect of 3,4-methylendioxymethamphetamine (MDMA, “ecstasy”) on dopamine transmission in the nucleus accumbens shell and core. Brain Res 1055(1–2):143–148

    Article  CAS  PubMed  Google Scholar 

  • Cahir M et al (2007) Acute and chronic tryptophan depletion differentially regulate central 5-HT1A and 5-HT 2A receptor binding in the rat. Psychopharmacology 190(4):497–506

    Article  CAS  PubMed  Google Scholar 

  • Callaway CW, Wing LL, Geyer MA (1990) Serotonin release contributes to the locomotor stimulant effects of 3,4-methylenedioxymethamphetamine in rats. J Pharmacol Exp Ther 254(2):456–464

    CAS  PubMed  Google Scholar 

  • Capela JP et al (2009) Molecular and cellular mechanisms of ecstasy-induced neurotoxicity: an overview. Mol Neurobiol 39(3):210–271

    Article  CAS  PubMed  Google Scholar 

  • Carati C, Schenk S (2011) Role of dopamine D1- and D2-like receptor mechanisms in drug-seeking following methamphetamine self-administration in rats. Pharmacol Biochem Behav 98(3):449–454

    Article  CAS  PubMed  Google Scholar 

  • Childress AR et al (1993) Cue reactivity and cue reactivity interventions in drug dependence. NIDA Res Monogr 137:73–95

    CAS  PubMed  Google Scholar 

  • Clark L, Cools R, Robbins TW (2004) The neuropsychology of ventral prefrontal cortex: decision-making and reversal learning. Brain Cogn 55(1):41–53

    Article  CAS  PubMed  Google Scholar 

  • Cole JC, Sumnall HR (2003) The pre-clinical behavioural pharmacology of 3,4-methylenedioxymethamphetamine (MDMA). Neurosci Biobehav Rev 27(3):199–217

    Article  CAS  PubMed  Google Scholar 

  • Colussi-Mas J, Schenk S (2008) Acute and sensitized response to 3,4-methylenedioxymethamphetamine in rats: different behavioral profiles reflected in different patterns of Fos expression. Eur J Neurosci 28(9):1895–1910

    Article  PubMed  Google Scholar 

  • Colussi-Mas J et al (2010) Drug-seeking in response to a priming injection of MDMA in rats: relationship to initial sensitivity to self-administered MDMA and dorsal striatal dopamine. Int J Neuropsychopharmacol 13(10):1315–1327

    Article  CAS  PubMed  Google Scholar 

  • Cottler LB et al (2001) Ecstasy abuse and dependence among adolescents and young adults: applicability and reliability of DSM-IV criteria. Hum Psychopharmacol 16(8):599–606

    Article  CAS  PubMed  Google Scholar 

  • Cottler LB, Leung KS, Abdallah AB (2009) Test-re-test reliability of DSM-IV adopted criteria for 3,4-methylenedioxymethamphetamine (MDMA) abuse and dependence: a cross-national study. Addiction 104(10):1679–1690

    Article  PubMed  PubMed Central  Google Scholar 

  • Cowan RL (2007) Neuroimaging research in human MDMA users: a review. Psychopharmacology 189(4):539–556

    Article  CAS  PubMed  Google Scholar 

  • Crombag HS et al (2008) Review. Context-induced relapse to drug-seeking: a review. Philos Trans R Soc Lond B Biol Sci 363(1507):3233–3243

    Article  PubMed  PubMed Central  Google Scholar 

  • Cunningham KA, Anastasio NC (2014) Serotonin at the nexus of impulsivity and cue reactivity in cocaine addiction. Neuropharmacology 76:460–478

    Article  CAS  PubMed  Google Scholar 

  • Curran HV, Travill RA (1997) Mood and cognitive effects of +/−3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’): week-end ‘high’ followed by mid-week low. Addiction 92(7):821–831

    CAS  PubMed  Google Scholar 

  • Dalley JW et al (2007) Nucleus accumbens D2/3 receptors predict trait impulsivity and cocaine reinforcement. Science 315(5816):1267–1270

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Daniela E et al (2004) Effect of SCH 23390 on (+/−)-3,4-methylenedioxymethamphetamine hyperactivity and self-administration in rats. Pharmacol Biochem Behav 77(4):745–750

    Article  CAS  PubMed  Google Scholar 

  • Daniela E, Gittings D, Schenk S (2006) Conditioning following repeated exposure to MDMA in rats: role in the maintenance of MDMA self-administration. Behav Neurosci 120(5):1144–1150

    Article  CAS  PubMed  Google Scholar 

  • Davis AK, Rosenberg H (2014) The prevalence, intensity, and assessment of craving for MDMA/ecstasy in recreational users. J Psychoactive Drugs 46(2):154–161

    Article  PubMed  Google Scholar 

  • De Wit H (2009) Impulsivity as a determinant and consequence of drug use: a review of underlying processes. Addict Biol 14(1):22–31

    Article  PubMed  Google Scholar 

  • Degenhardt L, Bruno R, Topp L (2010) Is ecstasy a drug of dependence? Drug Alcohol Depend 107(1):1–10

    Article  CAS  PubMed  Google Scholar 

  • Di Ciano P, Everitt BJ (2004) Conditioned reinforcing properties of stimuli paired with self-administered cocaine, heroin or sucrose: implications for the persistence of addictive behaviour. Neuropharmacology 47(Suppl 1):202–213

    Article  PubMed  CAS  Google Scholar 

  • Di Giovanni G, Esposito E, Di Matteo V (2010) Role of serotonin in central dopamine dysfunction. CNS Neurosci Ther 16(3):179–194

    Article  PubMed  CAS  Google Scholar 

  • Di Iorio CR et al (2012) Evidence for chronically altered serotonin function in the cerebral cortex of female 3,4-methylenedioxymethamphetamine polydrug users. Arch Gen Psychiatry 69(4):399–409

    Article  PubMed  CAS  Google Scholar 

  • Diergaarde L et al (2008) Impulsive choice and impulsive action predict vulnerability to distinct stages of nicotine seeking in rats. Biol Psychiatry 63(3):301–308

    Article  CAS  PubMed  Google Scholar 

  • Doherty MD, Pickel VM (2000) Ultrastructural localization of the serotonin 2A receptor in dopaminergic neurons in the ventral tegmental area. Brain Res 864(2):176–185

    Article  CAS  PubMed  Google Scholar 

  • Economidou D et al (2009) High impulsivity predicts relapse to cocaine-seeking after punishment-induced abstinence. Biol Psychiatry 65(10):851–856

    Article  CAS  PubMed  Google Scholar 

  • Esposito E, Di Matteo V, Di Giovanni G (2008) Serotonin-dopamine interaction: an overview. Prog Brain Res 172:3–6

    Article  CAS  PubMed  Google Scholar 

  • Evenden JL (1999) Varieties of impulsivity. Psychopharmacology 146(4):348–361

    Article  CAS  PubMed  Google Scholar 

  • Evenden J, Ryan C (1999) The pharmacology of impulsive behaviour in rats VI: the effects of ethanol and selective serotonergic drugs on response choice with varying delays of reinforcement. Psychopharmacology 146(4):413–421

    Article  CAS  PubMed  Google Scholar 

  • Everitt BJ, Robbins TW (2000) Second-order schedules of drug reinforcement in rats and monkeys: measurement of reinforcing efficacy and drug-seeking behaviour. Psychopharmacology 153(1):17–30

    Article  CAS  PubMed  Google Scholar 

  • Everitt BJ, Robbins TW (2005) Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nat Neurosci 8(11):1481–1489

    Article  CAS  PubMed  Google Scholar 

  • Everitt BJ, Robbins TW (2013) From the ventral to the dorsal striatum: devolving views of their roles in drug addiction. Neurosci Biobehav Rev 37(9):1946–1954

    Google Scholar 

  • Everitt BJ et al (2008) Review. Neural mechanisms underlying the vulnerability to develop compulsive drug-seeking habits and addiction. Philos Trans R Soc Lond B Biol Sci 363(1507):3125–3135

    Article  PubMed  PubMed Central  Google Scholar 

  • Fantegrossi WE et al (2004) Behavioral and neurochemical consequences of long-term intravenous self-administration of MDMA and its enantiomers by rhesus monkeys. Neuropsychopharmacology 29(7):1270–1281

    Article  CAS  PubMed  Google Scholar 

  • Fink LH et al (2015) Individual differences in impulsive action reflect variation in the cortical serotonin 5-HT2A receptor system. Neuropsychopharmacology

    Google Scholar 

  • Fletcher PJ, Robinson SR, Slippoy DL (2001) Pre-exposure to (+/−)3,4-methylenedioxy-methamphetamine (MDMA) facilitates acquisition of intravenous cocaine self-administration in rats. Neuropsychopharmacology 25(2):195–203

    Article  CAS  PubMed  Google Scholar 

  • Fletcher PJ et al (2007) Opposing effects of 5-HT2A and 5-HT2C receptor antagonists in the rat and mouse on premature responding in the five-choice serial reaction time test. Psychopharmacology 195(2):223–234

    Article  CAS  PubMed  Google Scholar 

  • Gabbott PL et al (2005) Prefrontal cortex in the rat: projections to subcortical autonomic, motor, and limbic centers. J Comp Neurol 492(2):145–177

    Article  PubMed  Google Scholar 

  • Gerra G et al (2003) Hypothalamic-pituitary-adrenal axis responses to stress in subjects with 3,4-methylenedioxy-methamphetamine (‘ecstasy’) use history: correlation with dopamine receptor sensitivity. Psychiatry Res 120(2):115–124

    Article  CAS  PubMed  Google Scholar 

  • Gold LH, Hubner CB, Koob GF (1989) A role for the mesolimbic dopamine system in the psychostimulant actions of MDMA. Psychopharmacology 99(1):40–47

    Article  CAS  PubMed  Google Scholar 

  • Grimm JW et al (2001) Neuroadaptation. Incubation of cocaine craving after withdrawal. Nature 412(6843):141–142

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heal DJ et al (1985) Intracerebroventricular administration of 5,7-dihydroxytryptamine to mice increases both head-twitch response and the number of cortical 5-HT2 receptors. Neuropharmacology 24(12):1201–1205

    Article  CAS  PubMed  Google Scholar 

  • Homberg JR (2012) Serotonin and decision making processes. Neurosci Biobehav Rev 36(1):218–236

    Article  CAS  PubMed  Google Scholar 

  • Hoover WB, Vertes RP (2007) Anatomical analysis of afferent projections to the medial prefrontal cortex in the rat. Brain Struct Funct 212(2):149–179

    Article  PubMed  Google Scholar 

  • Hopper JW et al (2006) Incidence and patterns of polydrug use and craving for ecstasy in regular ecstasy users: an ecological momentary assessment study. Drug Alcohol Depend 85(3):221–235

    Article  CAS  PubMed  Google Scholar 

  • Hoyer D, Hannon JP, Martin GR (2002) Molecular, pharmacological and functional diversity of 5-HT receptors. Pharmacol Biochem Behav 71(4):533–554

    Article  CAS  PubMed  Google Scholar 

  • Huxster JK, Pirona A, Morgan MJ (2006) The sub-acute effects of recreational ecstasy (MDMA) use: a controlled study in humans. J Psychopharmacol 20(2):281–290

    Article  PubMed  Google Scholar 

  • Jasinska AJ et al (2014) Factors modulating neural reactivity to drug cues in addiction: a survey of human neuroimaging studies. Neurosci Biobehav Rev 38:1–16

    Article  PubMed  Google Scholar 

  • Johanson CE et al (2006) Discriminative stimulus effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans trained to discriminate among d-amphetamine, meta-chlorophenylpiperazine and placebo. Drug Alcohol Depend 81(1):27–36

    Article  CAS  PubMed  Google Scholar 

  • Kalivas PW (2008) Addiction as a pathology in prefrontal cortical regulation of corticostriatal habit circuitry. Neurotox Res 14(2–3):185–189

    Article  PubMed  Google Scholar 

  • Kalivas PW (2009) The glutamate homeostasis hypothesis of addiction. Nat Rev Neurosci 10(8):561–572

    Article  CAS  PubMed  Google Scholar 

  • Kalivas PW, Duffy P, White SR (1998) MDMA elicits behavioral and neurochemical sensitization in rats. Neuropsychopharmacology 18(6):469–479

    Article  CAS  PubMed  Google Scholar 

  • Kirisci L et al (2007) Developmental trajectory classes in substance use disorder etiology. Psychol Addict Behav 21(3):287

    Article  PubMed  Google Scholar 

  • Kirkpatrick MG et al (2012) A direct comparison of the behavioral and physiological effects of methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) in humans. Psychopharmacology 219(1):109–122

    Article  CAS  PubMed  Google Scholar 

  • Kirkpatrick MG et al (2014) MDMA effects consistent across laboratories. Psychopharmacology 231(19):3899–3905

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koffarnus MN, Woods JH (2013) Individual differences in discount rate are associated with demand for self-administered cocaine, but not sucrose. Addict Biol 18(1):8–18

    Article  CAS  PubMed  Google Scholar 

  • Koob GF, Volkow ND (2010) Neurocircuitry of addiction. Neuropsychopharmacology 35(1):217–238

    Article  PubMed  Google Scholar 

  • Koskinen T, Sirviö J (2001) Studies on the involvement of the dopaminergic system in the 5-HT 2 agonist (DOI)-induced premature responding in a five-choice serial reaction time task. Brain Res Bull 54(1):65–75

    Article  CAS  PubMed  Google Scholar 

  • Koskinen T, Ruotsalainen S, Sirviö J (2000a) The 5-HT 2 receptor activation enhances impulsive responding without increasing motor activity in rats. Pharmacol Biochem Behav 66(4):729–738

    Article  CAS  PubMed  Google Scholar 

  • Koskinen T et al (2000b) Activation of 5-HT 2A receptors impairs response control of rats in a five-choice serial reaction time task. Neuropharmacology 39(3):471–481

    Article  CAS  PubMed  Google Scholar 

  • Koskinen T, Haapalinna A, Sirvi J (2003) α-adrenoceptor-mediated modulation of 5-HT2 receptor agonist induced impulsive responding in a 5-choice serial reaction time task. Pharmacol Toxicol 92(5):214–225

    Article  CAS  PubMed  Google Scholar 

  • Lichtigfeld FJ, Gillman MA (1998) Antidepressants are not drugs of abuse or dependence. Postgrad Med J 74(875):529–532

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liechti ME, Vollenweider FX (2000) Acute psychological and physiological effects of MDMA (“Ecstasy”) after haloperidol pretreatment in healthy humans. Eur Neuropsychopharmacol 10(4):289–295

    Article  CAS  PubMed  Google Scholar 

  • Liechti ME et al (2000) Psychological and physiological effects of MDMA (“Ecstasy”) after pretreatment with the 5-HT(2) antagonist ketanserin in healthy humans. Neuropsychopharmacology 23(4):396–404

    Article  CAS  PubMed  Google Scholar 

  • Lizarraga LE et al (2014) Serotonin reuptake transporter deficiency modulates the acute thermoregulatory and locomotor activity response to 3,4-(+/−)-methylenedioxymethamphetamine, and attenuates depletions in serotonin levels in SERT-KO rats. Toxicol Sci 139(2):421–431

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Loos M et al (2013) Enhanced alcohol self-administration and reinstatement in a highly impulsive, inattentive recombinant inbred mouse strain. Front Behav Neurosci 7

    Google Scholar 

  • Ludwig V, Mihov Y, Schwarting RK (2008) Behavioral and neurochemical consequences of multiple MDMA administrations in the rat: role of individual differences in anxiety-related behavior. Behav Brain Res 189(1):52–64

    Article  CAS  PubMed  Google Scholar 

  • Marchant NJ et al (2014) Role of corticostriatal circuits in context-induced reinstatement of drug-seeking. Brain Res

    Google Scholar 

  • McCann UD, Eligulashvili V, Ricaurte GA (2000) (+/−)3,4-Methylenedioxymethamphetamine (‘Ecstasy’)-induced serotonin neurotoxicity: clinical studies. Neuropsychobiology 42(1):11–16

    Article  CAS  PubMed  Google Scholar 

  • McCann UD et al (2008) Positron emission tomographic studies of brain dopamine and serotonin transporters in abstinent (+/−)3,4-methylenedioxymethamphetamine (“ecstasy”) users: relationship to cognitive performance. Psychopharmacology 200(3):439–450

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McCreary AC, Bankson MG, Cunningham KA (1999) Pharmacological studies of the acute and chronic effects of (+)-3,4-methylenedioxymethamphetamine on locomotor activity: role of 5-hydroxytryptamine(1A) and 5-hydroxytryptamine(1B/1D) receptors. J Pharmacol Exp Ther 290(3):965–973

    CAS  PubMed  Google Scholar 

  • McKetin R et al (2014) The effect of the ecstasy ‘come-down’ on the diagnosis of ecstasy dependence. Drug Alcohol Depend 139:26–32

    Article  CAS  PubMed  Google Scholar 

  • Mengod G et al (1990) Localization of the mRNA for the 5-HT2 receptor by in situ hybridization histochemistry. Correlation with the distribution of receptor sites. Brain Res 524(1):139–143

    Article  CAS  PubMed  Google Scholar 

  • Modi GM et al (2006) Chronic exposure to MDMA (Ecstasy) elicits behavioral sensitization in rats but fails to induce cross-sensitization to other psychostimulants. Behav Brain Funct 2:1

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Moreno-Sanz G et al (2009) Administration of MDMA to ethanol-deprived rats increases ethanol operant self-administration and dopamine release during reinstatement. Int J Neuropsychopharmacol 12(7):929–940

    Article  CAS  PubMed  Google Scholar 

  • Morgan MJ (1998) Recreational use of “ecstasy”(MDMA) is associated with elevated impulsivity. Neuropsychopharmacology 19(4):252–264

    Article  CAS  PubMed  Google Scholar 

  • Oakly AC et al (2014) A genetic deletion of the serotonin transporter greatly enhances the reinforcing properties of MDMA in rats. Mol Psychiatry 19(5):534–535

    Article  CAS  PubMed  Google Scholar 

  • Obradovic T, Imel KM, White SR (1996) Methylenedioxymethamphetamine-induced inhibition of neuronal firing in the nucleus accumbens is mediated by both serotonin and dopamine. Neuroscience 74(2):469–481

    Article  CAS  PubMed  Google Scholar 

  • Parrott AC (2005) Chronic tolerance to recreational MDMA (3,4-methylenedioxymethamphetamine) or ecstasy. J Psychopharmacol 19(1):71–83

    Article  CAS  PubMed  Google Scholar 

  • Parrott AC (2013) Human psychobiology of MDMA or ‘Ecstasy’: an overview of 25 years of empirical research. Hum Psychopharmacol 28(4):289–307

    Article  CAS  PubMed  Google Scholar 

  • Parrott AC, MDMA is certainly damaging after 25 years of empirical research: A reply and refutation of Doblin et al (2014). Human Psychopharmacology, 2014. 29(2): p. 109–119

    Google Scholar 

  • Passetti F, Dalley JW, Robbins TW (2003) Double dissociation of serotonergic and dopaminergic mechanisms on attentional performance using a rodent five-choice reaction time task. Psychopharmacology 165(2):136–145

    Article  CAS  PubMed  Google Scholar 

  • Pattij T, Vanderschuren LJ (2008) The neuropharmacology of impulsive behaviour. Trends Pharmacol Sci 29(4):192–199

    Article  CAS  PubMed  Google Scholar 

  • Pazos A, Palacios JM (1985) Quantitative autoradiographic mapping of serotonin receptors in the rat brain. I. Serotonin-1 receptors. Brain Res 346(2):205–230

    Article  CAS  PubMed  Google Scholar 

  • Peroutka SJ, Newman H, Harris H (1988) Subjective effects of 3,4-methylenedioxymethamphetamine in recreational users. Neuropsychopharmacology 1(4):273–277

    CAS  PubMed  Google Scholar 

  • Perry JL, Carroll ME (2008) The role of impulsive behavior in drug abuse. Psychopharmacology 200(1):1–26

    Article  CAS  PubMed  Google Scholar 

  • Perry JL et al (2005) Impulsivity (delay discounting) as a predictor of acquisition of IV cocaine self-administration in female rats. Psychopharmacology 178(2–3):193–201

    Article  CAS  PubMed  Google Scholar 

  • Perry JL, Nelson SE, Carroll ME (2008a) Impulsive choice as a predictor of acquisition of IV cocaine self-administration and reinstatement of cocaine-seeking behavior in male and female rats. Exp Clin Psychopharmacol 16(2):165–177

    Article  PubMed  Google Scholar 

  • Perry JL, Nelson SE, Carroll ME (2008b) Impulsive choice as a predictor of acquisition of IV cocaine self-administration and reinstatement of cocaine-seeking behavior in male and female rats. Experiment Clin Psychopharmacol 16(2):165

    Article  Google Scholar 

  • Poulos CX, Le A, Parker J (1995) Impulsivity predicts individual susceptibility to high levels of alcohol self-administration. Behav Pharmacol

    Google Scholar 

  • Regier PS et al (2014) Cocaine-, caffeine-, and stress-evoked cocaine reinstatement in high vs. low impulsive rats: treatment with allopregnanolone. Drug Alcohol Depend 143:58–64

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reneman L et al (2002) Use of amphetamine by recreational users of ecstasy (MDMA) is associated with reduced striatal dopamine transporter densities: a [123I]beta-CIT SPECT study–preliminary report. Psychopharmacology 159(3):335–340

    Article  CAS  PubMed  Google Scholar 

  • Reveron ME, Maier EY, Duvauchelle CL (2010) Behavioral, thermal and neurochemical effects of acute and chronic 3,4-methylenedioxymethamphetamine (“Ecstasy”) self-administration. Behav Brain Res 207(2):500–507

    Article  CAS  PubMed  Google Scholar 

  • Ricaurte GA, Yuan J, McCann UD (2000) (+/−)3,4-methylenedioxymethamphetamine (‘Ecstasy’)-induced serotonin neurotoxicity: studies in animals. Neuropsychobiology 42(1):5–10

    Article  CAS  PubMed  Google Scholar 

  • Ritz MC, Kuhar MJ (1989) Relationship between self-administration of amphetamine and monoamine receptors in brain: comparison with cocaine. J Pharmacol Exp Ther 248(3):1010–1017

    CAS  PubMed  Google Scholar 

  • Robbins T (2002) The 5-choice serial reaction time task: behavioural pharmacology and functional neurochemistry. Psychopharmacology 163(3–4):362–380

    Article  CAS  PubMed  Google Scholar 

  • Robinson TE, Becker JB (1986) Enduring changes in brain and behavior produced by chronic amphetamine administration: a review and evaluation of animal models of amphetamine psychosis. Brain Res 396(2):157–198

    Article  CAS  PubMed  Google Scholar 

  • Rothman RB, Baumann MH (2006) Balance between dopamine and serotonin release modulates behavioral effects of amphetamine-type drugs. Ann NY Acad Sci 1074:245–260

    Article  CAS  PubMed  Google Scholar 

  • Ruotsalainen S et al (1997) Differential effects of three 5-HT receptor antagonists on the performance of rats in attentional and working memory tasks. Eur Neuropsychopharmacol 7(2):99–108

    Article  CAS  PubMed  Google Scholar 

  • Schenk S (2011) MDMA (“ecstasy”) abuse as an example of dopamine neuroplasticity. Neurosci Biobehav Rev 35(5):1203–1218

    Article  CAS  PubMed  Google Scholar 

  • Schenk S, Bradbury S (2015) Persistent sensitisation to the locomotor activating effects of MDMA following MDMA self-administration in rats. Pharmacol Biochem Behav 132:103–107

    Article  CAS  PubMed  Google Scholar 

  • Schenk S, Partridge B (2001) Influence of a conditioned light stimulus on cocaine self-administration in rats. Psychopharmacology 154(4):390–396

    Article  CAS  PubMed  Google Scholar 

  • Schenk S et al (2003) Development, maintenance and temporal pattern of self-administration maintained by ecstasy (MDMA) in rats. Psychopharmacology 169(1):21–27

    Article  CAS  PubMed  Google Scholar 

  • Schenk S et al (2007) MDMA self-administration in rats: acquisition, progressive ratio responding and serotonin transporter binding. Eur J Neurosci 26(11):3229–3236

    Article  PubMed  Google Scholar 

  • Schindler CW, Panlilio LV, Goldberg SR (2002) Second-order schedules of drug self-administration in animals. Psychopharmacology 163(3–4):327–344

    Article  CAS  PubMed  Google Scholar 

  • Schultz W (1997) Dopamine neurons and their role in reward mechanisms. Curr Opin Neurobiol 7(2):191–197

    Article  CAS  PubMed  Google Scholar 

  • Shankaran M, Gudelsky GA (1999) A neurotoxic regimen of MDMA suppresses behavioral, thermal and neurochemical responses to subsequent MDMA administration. Psychopharmacology 147(1):66–72

    Article  CAS  PubMed  Google Scholar 

  • Sher KJ, Bartholow BD, Wood MD (2000) Personality and substance use disorders: a prospective study. J Consult Clin Psychol 68(5):818

    Article  CAS  PubMed  Google Scholar 

  • Shortall SE et al (2013) Behavioural and neurochemical comparison of chronic intermittent cathinone, mephedrone and MDMA administration to the rat. Eur Neuropsychopharmacol 23(9):1085–1095

    Article  CAS  PubMed  Google Scholar 

  • Smith JL et al (2014) Deficits in behavioural inhibition in substance abuse and addiction: a meta-analysis. Drug Alcohol Depend 145:1–33

    Article  PubMed  Google Scholar 

  • Soar K, Turner JJ, Parrott AC (2006) Problematic versus non-problematic ecstasy/MDMA use: the influence of drug usage patterns and pre-existing psychiatric factors. J Psychopharmacol 20(3):417–424

    Article  CAS  PubMed  Google Scholar 

  • Tai YF et al (2011) Persistent nigrostriatal dopaminergic abnormalities in ex-users of MDMA (‘Ecstasy’): an 18F-dopa PET study. Neuropsychopharmacology 36(4):735–743

    Article  CAS  PubMed  Google Scholar 

  • Talpos JC, Wilkinson LS, Robbins TW (2006) A comparison of multiple 5-HT receptors in two tasks measuring impulsivity. J Psychopharm 20(1):47–58

    Article  CAS  Google Scholar 

  • Tancer ME, Johanson CE (2001) The subjective effects of MDMA and mCPP in moderate MDMA users. Drug Alcohol Depend 65(1):97–101

    Article  CAS  PubMed  Google Scholar 

  • Tancer M, Johanson CE (2003) Reinforcing, subjective, and physiological effects of MDMA in humans: a comparison with d-amphetamine and mCPP. Drug Alcohol Depend 72(1):33–44

    Article  CAS  PubMed  Google Scholar 

  • Tarter RE et al (2007) Modeling the pathways linking childhood hyperactivity and substance use disorder in young adulthood. Psychol Addict Behav 21(2):266

    Article  PubMed  Google Scholar 

  • Topp L et al (1999) Ecstasy use in Australia: patterns of use and associated harm. Drug Alcohol Depend 55(1–2):105–115

    Article  CAS  PubMed  Google Scholar 

  • Tzschentke TM (1998) Measuring reward with the conditioned place preference paradigm: a comprehensive review of drug effects, recent progress and new issues. Prog Neurobiol 56(6):613–672

    Article  CAS  PubMed  Google Scholar 

  • Urban NB et al (2012) Sustained recreational use of ecstasy is associated with altered pre and postsynaptic markers of serotonin transmission in neocortical areas: a PET study with [(1)(1)C]DASB and [(1)(1)C]MDL 100907. Neuropsychopharmacology 37(6):1465–1473

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Volkow ND, Baler RD (2014) Addiction science: uncovering neurobiological complexity. Neuropharmacology 76:235–49

    Google Scholar 

  • Voorn P et al (2004) Putting a spin on the dorsal-ventral divide of the striatum. Trends Neurosci 27(8):468–474

    Article  CAS  PubMed  Google Scholar 

  • Wee S, Woolverton WL (2006) Self-administration of mixtures of fenfluramine and amphetamine by rhesus monkeys. Pharmacol Biochem Behav 84(2):337–343

    Article  CAS  PubMed  Google Scholar 

  • Wee S et al (2005) Relationship between the serotonergic activity and reinforcing effects of a series of amphetamine analogs. J Pharmacol Exp Ther 313(2):848–854

    Article  CAS  PubMed  Google Scholar 

  • Weiss F et al (1992) Neurochemical correlates of cocaine and ethanol self-administration. Ann NY Acad Sci 654:220–241

    Article  CAS  PubMed  Google Scholar 

  • White SR, Duffy P, Kalivas PW (1994) Methylenedioxymethamphetamine depresses glutamate-evoked neuronal firing and increases extracellular levels of dopamine and serotonin in the nucleus accumbens in vivo. Neuroscience 62(1):41–50

    Article  CAS  PubMed  Google Scholar 

  • Winstanley CA et al (2004) 5-HT2A and 5-HT2C receptor antagonists have opposing effects on a measure of impulsivity: interactions with global 5-HT depletion. Psychopharmacology 176(3–4):376–385

    Article  CAS  PubMed  Google Scholar 

  • Yang PB, Atkins KD, Dafny N (2011) Behavioral sensitization and cross-sensitization between methylphenidate amphetamine, and 3,4-methylenedioxymethamphetamine (MDMA) in female SD rats. Eur J Pharmacol 661(1–3):72–85

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yen CF, Hsu SY (2007) Symptoms of ecstasy dependence and correlation with psychopathology in Taiwanese adolescents. J Nerv Ment Dis 195(10):866–869

    Article  PubMed  Google Scholar 

  • Zlebnik NE, Carroll ME (2015) Effects of the combination of wheel running and atomoxetine on cue-and cocaine-primed reinstatement in rats selected for high or low impulsivity. Psychopharmacology 232(6):1049–1059

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. School of Psychology, Victoria University of Wellington, Wellington, New Zealand

    Susan Schenk & Dane Aronsen

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  1. Susan Schenk
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  2. Dane Aronsen
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Correspondence to Susan Schenk .

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  1. National Drug and Alcohol Research Centre, University of New South Wales, Sydney, New South Wales, Australia

    Suzanne Nielsen

  2. University of Tasmania School of Psychology, Launceston, Tasmania, Australia

    Raimondo Bruno

  3. Victoria University of Wellington School of Psychology, Wellington, New Zealand

    Susan Schenk

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Schenk, S., Aronsen, D. (2015). Contribution of Impulsivity and Serotonin Receptor Neuroadaptations to the Development of an MDMA (‘Ecstasy’) Substance Use Disorder. In: Nielsen, S., Bruno, R., Schenk, S. (eds) Non-medical and illicit use of psychoactive drugs. Current Topics in Behavioral Neurosciences, vol 34. Springer, Cham. https://doi.org/10.1007/7854_2015_421

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