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Neurotoxicity Research

, Volume 3, Issue 1, pp 85–99 | Cite as

Experimental studies on 3,4-methylenedioxymethamphetamine (MDMA, “ECSTASY”) and its potential to damage brain serotonin neurons

  • George A. Ricaurte
  • Una D. McCann
Article

Abstract

A number of drugs that fall into the broad category of “ring-substituted amphetamines” have been found to be neurotoxic toward brain monoamine neurons in animals. Several of these drugs, including (3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) and methamphetamine (“speed”) and fenfluramine (“Pondimin”) have been used or abused by humans. A growing body of evidence indicates that humans, like animals, are susceptible to substituted amphetamine-induced neurotoxic injury, and that consequences of this injury can be subtle. This article will review the effects of ring-substituted amphetamine analogs on brain monoamine neurons, using MDMA as the prototype. Studies documenting MDMA neurotoxic potential toward brain serotonin (5-HT) neurons in animals are summarized first. Human MDMA studies are then discussed, beginning with a consideration of methodological challenges in evaluating the status of 5-HT neurons in the living human brain. Recent findings indicating possible functional alterations in brain serotonergic systems in humans with a history of extensive MDMA exposure are then presented, including some new findings on sleep and personality in abstinent MDMA users.

Keywords

MDMA drug abuse CNS amphetamines serotonin neurotoxicity 

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References

  1. Allen, R., McCann, U.D. and Ricaurte, G.A. (1993) Sleep in abstinent users of MDMA.Sleep. 16, 560–564.PubMedGoogle Scholar
  2. Asberg, M., Thoren, P. and Traskman, L. (1976) “Serotonin Depression” — a biochemical subgroup within the affective disorders?Science 191, 478–480.PubMedCrossRefGoogle Scholar
  3. Aulakh, C.S., Hill, J.L. and Murphy, D.L. (1992) Effects of various serotonin receptor subtype selective antagonists alone and on m-CPP-induced neuroendocrine changes in rats.J. Pharmacol. Exp. Ther. 263, 588–595.PubMedGoogle Scholar
  4. Battaglia, G., Yeh, S.Y., O’Hearn, E., Molliver, M.E., Kuhar, M.J. and DeSouza, E.B. (1987) 3,4-Methylenedioxymeth-amphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites.J. Pharmacol. Exp. Ther. 242, 911–916.PubMedGoogle Scholar
  5. Battaglia, G., Yeh, S.Y. and DeSouza, E.B. (1988) MDMA-induced neurotoxicity: Parameters of degeneration and recovery of brain serotonin neurons.Pharmacol. Biochem. and Behav. 29, 269–274.CrossRefGoogle Scholar
  6. Berendsen, H.H.G., Broekamp, C.L.E. and Van Delft A.M.L. (1990) Denervation supersensitivity of 5HT1C — but not of 5HT1A — and 5HTj.Psychopharmacology 101 (suppl.), 55.CrossRefGoogle Scholar
  7. Bert, J. (1972) Action de la p-chlorophenylanlanine sur le sommeil du babouin papio.Electroencephalogr. Clin. Neurophysiol. 33, 99–103.PubMedCrossRefGoogle Scholar
  8. Bertilsson, L., Asberg, M., Lantto, O., Scalia-Tomba, G., Traskman-Bendz, L. and Tybring, G. (1982) Gradients of monoamine metabolites and Cortisol in cerebrospinal fluid of psychiatric patients and healthy controls.Psychiatry Res.6, 77–83.PubMedCrossRefGoogle Scholar
  9. Bolla, K.I., McCann, U.D. and Ricaurte, G.A. (1998) Impaired memory function in abstinent MDMA (“Ecstasy”) users,Neurology 51(6), 1532–1537.PubMedGoogle Scholar
  10. Bowers, M.B. (1974) Lumbar CSF 5-hydroxyindoleacetic acid and homovanillic acid in affective syndromes.J. Nervous Mental Disease 158(5), 325–330.CrossRefGoogle Scholar
  11. Bowers, M.B. and Gerbode, F.A. (1968) Relationship of monoamine metabolites in human cerebrospinal fluid to age.Nature 19, 1256–1257.CrossRefGoogle Scholar
  12. Brewerton, T.D., Berrettini, W.H., Nurnberger, J.I. and Linnoila, M. (1987) Analysis of seasonal fluctuations of CSF monoamine metabolites and neuropeptides in normal controls: findings with 5-HIAA and HVA.Psychiatry Res. 23, 257–265.CrossRefGoogle Scholar
  13. Brown, C.C., Horrom, N.J. and Wagman, A.M.I. (1979) Effects of L-tryptophan on sleep onset insomniacs.Waking Sleeping. 3, 101–108.PubMedGoogle Scholar
  14. Brown, G.L., Ebert, M.H. and Goyer, P.F. (1982) Aggression, suicide and serotonin: Relationships to CSF metabolites.Am. J. Psychiatry 139, 741–746.PubMedGoogle Scholar
  15. Brown, G.L., Goodwin, F.K., Ballenger, J.C., Goyer, P.F. and Major, L.F. (1979) Aggression in humans correlates with cerebrospinal fluid metabolites.Psychiatry Res.1, 131–139.PubMedCrossRefGoogle Scholar
  16. Buss, A.H. and Durkee, A. (1957) An inventory for assessing different kinds of hostility.J. Consulting Psychology,21(4), 343–349.CrossRefGoogle Scholar
  17. Callahan, P.M. and Cunningham, K.A. (1994) Involvement of 5-HT2C receptors in mediating the discriminative stimulus properties of m-chlorophenylpiperazine (m-CPP).Eur. J. Pharmacol. 257, 27–38.PubMedCrossRefGoogle Scholar
  18. Callahan, B.T., Hatzidimitriou, G., Yuan, J. and Ricaurte, G.A. (1998) Long-term effects of substituted-ampheta-mines on anterograde axonal transport from the rostral raphe nuclei.Soc. Neurosci. Abstr. 24: 1735.Google Scholar
  19. Charney, D.S., Goodman, W.K., Price, L.H., Woods, S.W., Rasmussen, S.A. and Henninger, G.R. (1988) Serotonergic function in obsessive-compulsive disorder: a comparison of the effects of tryptophan and m-chlorophenylpiperazine in patients and healthy subjects.Arch. Gen. Psychiatry 45, 177–185.PubMedGoogle Scholar
  20. Clemens, J.A. (1978) Effects of serotonin neurotoxins on pituitary hormone release.Ann. N. Y. Acad. Sci. 305, 399–410.PubMedCrossRefGoogle Scholar
  21. Coccaro, E.F. (1989) Central serotonin and impulsive aggression.Br. J. Psychiatry 155, 52–62.Google Scholar
  22. Calogero, A.E., Bagdy, G., Moncada, MX. and D’Agata, R. (1993) Effect of selective serotonin agonists on basal, corticotropin-releasing hormone- and vasopressin-induced ACTH release in vitro from rat pituitary cells.J. Endocrinol. 136, 381–387.PubMedCrossRefGoogle Scholar
  23. Chappell, W. and Mordenti, J. (1991) Extrapolation of toxico-logical and pharmacological data from animals to humans. In: Testa, B. (Eds),Advances in Drug Research (San Diego, CA: Academic Press), pp. 1–116.Google Scholar
  24. Charney, D.S., Woods, S.W., Goodman, W.K. and Henninger, G.R. (1987) Serotonin function in anxiety. II. Effects of the serotonin agonist m-CPP in panic disorder patients and healthy subjects.Arch. Gen. Psychiatry 45, 177–185.Google Scholar
  25. Commins, D.L., Vosmer, G., Virus, R., Woolverton, W., Schuster, C and Seiden, L. (1987) Biochemical and histological evidence that methylenedioxymethylamphetamine (MDMA) is toxic to neurons in the rat brain.J. Pharmacol. Exp. Ther. 241, 338–345.PubMedGoogle Scholar
  26. Conn, P.J. and Sanders-Bush, E. (1987) Relative efficacies of piperazones at the phosphoinosotide hydrolysis-linked serotonergic (5-HT-2 and 5-HT-1C) receptors.J. Pharmacol. Exp. Ther. 24, 552–557.Google Scholar
  27. Curzon, G., Joseph, M.H. and Knott, P.J. (1972) Effects of immobilization and food deprivation on rat brain tryptophan metabolism.J. Neurochem. 19, 1967–1974.PubMedCrossRefGoogle Scholar
  28. Eccleston, D., Ashcroft, G.W., Crawford, T.B., Stanton, J.B., Wood, D. and McTurk, P.H. (1970) Effect of tryptophan administration of 5-HIAA in cerebrospinal fluid in man.J. Neurol. Neurosurg. Psychiat. 33, 269–272.PubMedCrossRefGoogle Scholar
  29. Eriksson, E., Engberg, G., Bing, O., Nissbrandt, H. (1999) Effects of MCPP on the extracellular concentrations of serotonin and dopamine in the brain.Neuropsychophar-macology 20: 287–296.Google Scholar
  30. Eysenck, H.J., & Eysenck, S.B.G. (1976).Manual of the EPQ (Eysenck Personality Inventory). Educational and Industrial Testing Service, San Diego, CA.Google Scholar
  31. Finnegan, K.T., Ricaurte, G.A., Ritchie, L.D., Irwin, I., Per-outka, S.J. and Langston, J.W. (1988) Orally administered MDMA causes a long-term depletion of serotonin in rat brain.Brain Res.447(1), 141–144.PubMedCrossRefGoogle Scholar
  32. First, M.B., Spitzer, R.L., Gibbon, M. and Williams, J.B.W. (1998) Structured Clinical Interview for DSM-IV Axis I Disorders — Patient Edition (SCID I/P, Version 2.0).Biometrics Res. Google Scholar
  33. Fischer, C.A., Hatzidimitriou, G., Katz, J.L. and Ricaurte, G.A. (1995) Reorganization of ascending serotonin axon projections in animals previously exposed to the recreational drug 3,4-methylenedioxymethamphetamine.J. Neurosci. 15, 5476–5485.PubMedGoogle Scholar
  34. Florio, V., Scotti, A., Carolis, A. and Longo, V.G. (1968) Observations on the effect of d,l-parachlorophenyla-lanine on the electroencephalogram.Physiol. Behav. 3, 861–863.CrossRefGoogle Scholar
  35. Frey, K., Kilbourne, M. and Robinson, T. (1997) Reduced striatal vesicular monoamine transporters after neurotoxic but not after behaviorally-sensitizing doses of metham-phetamine.Eur. J. Pharmacol. 334, 273–279.PubMedCrossRefGoogle Scholar
  36. Fritschy, J. and Grzanna, R. (1992) Restoration of ascending noradrenergic projections by residual locu coeruleus neurons: Compensatory response to neurotoxin-induced cell death in the adult rat brain.J. Comparative Neurol. 321(3), 421–441.CrossRefGoogle Scholar
  37. Gaillard, J.M. and St. Hillaire-Kafi, S. (1985) Sleep, depression and the effects of antidepressant drugs,Acta Psy-chiatr. (Belg)85, 561–567.Google Scholar
  38. Gerra, G., Zaimovic, A., Giucastro, G., Maestri, D., Monica, C, Sartori, R., Caccavari, R. and Delsignore, R. (1998) Serotonergic function after (±) 3,4-methylenedioxymeth-amphetamine (“Ecstasy”) in humans.International Clin. Psychopharmacol. 13(l), l-9.Google Scholar
  39. Gibb, J. W., Hanson, G. R. and Johnson, M. Neurochemical mechanisms of toxicity. In: In: Amphetamine and its Analogs: Neuropsychopharmacology, Toxicology and Abuse, Cho A and Segal D (eds), Academic Press, New York, pp. 269–289, 1994.Google Scholar
  40. Griffiths, W.J., Lester, B.K., Coulter, J.D. and Williams H.L. (1972) Tryptophan and sleep in young adults.Psycho-physiology. 9, 345–356.Google Scholar
  41. Gustafson, E. and Moore, R. (1987) Noradrenaline neuron plasticity in developing rat brain: Effects of neonatal 6-hydroxydopamine demonstrated by dopamine-B-hydroxylase immunocytochemistry.Dev. Brain Res. 37, 143–155.CrossRefGoogle Scholar
  42. Halaris, A., Jones, B. and Moore, R. (1976) Axonal transport in serotonin neurons of the midbrain raphe.Brain Res. 107, 555–574.PubMedCrossRefGoogle Scholar
  43. Hartmann, E., Cravens, J. and List, S. (1974) Hypnotic effects of L-tryptophan.Arch. Gen. Psychiatry 31, 394–397.PubMedGoogle Scholar
  44. Hartmann, E. and Spinweber, C.L. (1979) Sleep induced by L-tryptophan.J. New. Ment. Dis. 167, 497–499.CrossRefGoogle Scholar
  45. Hatzidimitriou, G., McCann, U.D. and Ricaurte, G.A. (1999) Aberrant serotonin innervation in the forebrain of monkeys exposed to MDMA seven years previously: Factors influencing abnormal recovery,J. Neurosci. 19(12), 5096–5107.PubMedGoogle Scholar
  46. Hollander, E., Fay, M., Cohen, B., Campeas, R., Gorman, J.M. and Liebowitz, M.R. (1988) Serotonergic and noradrenergic sensitivity in obsessive-compulsive disorder: behavioral findings.Am. J. Psychiatry 145, 1015–1017.PubMedGoogle Scholar
  47. Insel, T.R., Battaglia, G., Johannessen, J.N., Marra, S. and De Souza, E.B. (1989) 3,4-Methylenedioxymethampheta-mine (“Ecstasy”) selectively destroys brain serotonin terminals in rhesus monkeys.J. Pharmacol. Exp. Ther. 249, 713–720.PubMedGoogle Scholar
  48. Jacupcevic, M., Lackovic, Z., Stefoski, D. and Bulat, M. (1977) Non-homogeneous distribution of 5-hydroxyindoleace-tic acid and homovanillic acid in the lumbar cerebrospinal fluid of man.J. Neurol. Sci. 31, 166–171.Google Scholar
  49. Johansson, B. and Roos, B-E. (1975) Concentration of monoamine metabolites in human lumbar and cisternal cerebrospinal fluid.Acta. Neurol. Scandinav. 52, 137–144.CrossRefGoogle Scholar
  50. Jouvet, M. (1969) Biogenic amines and the states of sleep.Science 163, 32–41.PubMedCrossRefGoogle Scholar
  51. Jouvet, M. and Renault, J. (1966) Insomnie persistente apres lesions de noyauz raphe chez de chat.Comp. Rend. Soc. Biol. (Paris)160, 1461–1465.Google Scholar
  52. Kahn, R.S., Asnis, G.M., Wetzler, S. and van Praag, H.M. (1988) Neuroendocrine evidence for serotonergic hypersensitivity in panic disorder.Psychopharmacology 96, 360–364.PubMedCrossRefGoogle Scholar
  53. Kato, Y., Nakai, Y., Imura, H., Chihara, K. and Ohgo, S. (1974) Effect of cyproheptadine on 5-hydroxytryptophan on plasma prolactin levels in man.J. Clin. Endocrin. Metab. 38, 696–703.Google Scholar
  54. Kennett, G.A. (1993) 5HT1C receptors and their therapeutic relevance.Curr. Opin. Invest. Drugs 2, 317–362.Google Scholar
  55. Kennett, G.A., Whitton, P., Shah, K. and Curzon, G. (1989) Anxiogenic-like effects of m-CPP and TFMPP in animal models are opposed by 5-HTlc receptor antagonists.Eur. J. Pharmacol. 164, 445–454.PubMedCrossRefGoogle Scholar
  56. Kennett, G.A., Wood, M.D., Glen, A., Grewal, S., Forbes, I., Gadre, A. and Blackburn, T.P. (1994) In vivo properties of SB 200646A, a 5-HT2C/2B receptor antagonist.Br. J. Pharmacol. 111, 797–802.PubMedGoogle Scholar
  57. Kerenyi, L., Szabo, Z., Scheffel, U., Mathews, W.B., Ravert, H.T., Szabo, K., Dannals, R.F. and Ricaurte, G.A. (1999) Assessment of serotonergic innervation with [nC]McN5652/PET: Validation of kinetic models in baboons.Soc. Nucl. Medicine 40(5): 115.Google Scholar
  58. Koella, W.P., Felstein, A. and Cziman, J.S. (1968) The effects of parachlorophenylalanine on the sleep of cats. Electro-encephalogr.Clin. Neurophysiol 25, 481–490.CrossRefGoogle Scholar
  59. Koslow, S.H., Maas, J.W., Bowden, C.L., Davis, J.M., Hanin, H. and Javaid, J. (1983) CSF and urinary biogenic amine metabolites in depression and mania.Arch. Gen. Psych. 40, 999–1010.Google Scholar
  60. Krystal, J.H., Price, L.H., Opsahl, C, Ricaurte, G.A. and Heninger, G.R. (1992) Chronic 3,4-methylenedioxymeth-amphetamine (MDMA) use: effects on mood and neuropsychological function.Amer. J. Drug Alcohol Abuse 18, 331–341.CrossRefGoogle Scholar
  61. Kuhn, CM., Vogel, R.A., Mailman, R.B., Mueller, R.A., Sehanberg, S.M. and Breese, G.R. (1981) Effect of 5,7-DHT on serotonergic control of prolactin secretion and behavior in rats.Psychopharmacology 73, 188–193.PubMedCrossRefGoogle Scholar
  62. Levitt, P. and Moore, R. (1980) Organization of brainstem noradrenaline hyperinnervation following neonatal 6-hydroxydopamine treatment in the rat.Anat. Embryol. 158, 133–150.PubMedCrossRefGoogle Scholar
  63. Linnoila, M., Virkkunen, M., Scheinin, M., Nautila, A., Rimon, R. and Goodwin, F.K. (1983) Low cerebrospinal fluid 5-hydroxyindoleacetic acid concentration differentiates impulsive from non-impulsive violent behavior.Life Sci. 33, 2609–2614.PubMedCrossRefGoogle Scholar
  64. Loranger, A.W. for the World Health Organization. (1995). International Personality Disorder Exam, DSM-IV Module. (1995) (Washington, DC: American Psychiatric Press).Google Scholar
  65. Lucki, I., Ward, H.R. and Frazer, A. (1989) Effect of l-(m-chlorophenyl)piperazine and 1-m-trifluoromethyl-phenyl)piperazine on locomotor activity.J. Pharmacol. Exp. Ther. 249, 155–164.PubMedGoogle Scholar
  66. Malven, P.V. (1993) Mammalian Neuroendocrinology, (Boca Raton, FL: CRC Press).Google Scholar
  67. Mazzola-Pomietto, P., Aulakh, C.S., Wozniak, K.M. and Murphy, D.L. (1996) Evidence that m-CPP-induced hyperthermia in rats is mediated by stimulation of 5-HT2c receptors.Psychopharmacology 123, 333–339.PubMedCrossRefGoogle Scholar
  68. McCann, U.D. and Ricaurte, G.A. (1993) Strategies for detecting subclinical monoamine depletions in humans. NIDAResearch Monogr. 136: 53–62.Google Scholar
  69. McCann, U.D., Mertl, M.M., Eligulashvili, V. and Ricaurte, G.A. (1999) Cognitive performance in (±) 3,4-methylene-dioxymethamphetamine (MDMA, “Ecstasy”) users: A controlled study.Psychopharmacology 143, 417–425.PubMedCrossRefGoogle Scholar
  70. McCann, U.D., Ridenour, A., Shaham, Y. and Ricaurte, G.A. (1994) Brain serotonergic neurotoxicity after MDMA (“Ecstasy”): A controlled study in humans.Neuropsy-chopharmacology 10, 129–138.Google Scholar
  71. McCann, U.D., Lowe, K.A., Ricaurte, G.A. (1997) Long-lasting effects of recreational drugs of abuse on the central nervous system.The Neuroscientist,3(6): 399–11.CrossRefGoogle Scholar
  72. McCann, U.D., Mertl, M.M., Murphy, D.L., Post, R.P. and Ricaurte, G.A. (1997) Neuroendocrine effects of intravenous metachlorophenylpiperazine in (±) 3,4-methylene-dioxymethamphetamine users.Amer. Psychiatric Assoc. New Research Program and Abstracts 147, (Abstract).Google Scholar
  73. McCann, U.D., Szabo, Z., Scheffel, U., Dannals, R.F. and Ricaurte, G.A. (1998) Positron Emission Tomographic evidence of toxic effect of MDMA (“Ecstasy”) on brain serotonin neurons in human beings.Lancet 352, 1433–1437.PubMedCrossRefGoogle Scholar
  74. McCann, U.D., Eligulashvili, V., Mertl, M., Murphy, D.L. and Ricaurte, G.A. (1999) Altered neuroendocrine and behavioral responses to m-chlorophenylpiperazine in 3,4-methylenedioxymethamphetamine (MDMA) users. Psychopharmacology, in press.Google Scholar
  75. Meltzer, H.Y. and Lowy, M. (1987) The serotonin hypothesis of depression. In: Meltzer, H. (Ed),Psychopharmacology: The Third Generation of Progress (New York, NY: Raven Press) pp. 513–526.Google Scholar
  76. Mendels, J., Frazer, A., Fitzgerald, R.G., Ramsey, T.A. and Stokes, J. (1972) Biogenic amine metabolites in cerebrospinal fluid of depressed and manic patients.Science 175, 1380–1382.PubMedCrossRefGoogle Scholar
  77. Molliver, M.E., Berger, U.V., Mamounas, L.A., Molliver, D.C., O’Hearn, E.G. and Wilson, M.A. (1990) Neurotoxicity of MDMA and related compounds: Anatomic studies.Ann. N.Y. Acad. Sci. 600, 640–664.CrossRefGoogle Scholar
  78. Mordenti, J. and Chappell, W. The use of interspecies scaling in toxicokinetics. In: Toxicokinetics in New Drug Development. Yacobi, A., Kelly, J., Batra, V. (Eds),Pergamon Press, New York, pp. 42–96, 1989.Google Scholar
  79. Morgan, M.M. (1999) Memory deficits associated with recreational use of “Ecstasy” (MDMA).Psychopharmacology 141, 30–36.PubMedCrossRefGoogle Scholar
  80. Murphy, D.L., Lesch, K.P., Aulakh, C.S. and Pigott, T.A. (1991) III. Serotonin-selective arylpiperazines with neuroendocrine, behavioral, temperature and cardiovascular effects in humans.Pharmacol. Rev. 43(4), 527–552.PubMedGoogle Scholar
  81. Murphy, D.L., Mueller, E.A., Hill, J.L., Tolliver, T.J. and Jacobsen, F.M. (1989) Comparative anxiogenic, neuroendocrine and other physiologic effects of m-chlorophenylpiperazine given intravenously or orally to healthy volunteers.Psychopharmacology 98, 275–282.PubMedCrossRefGoogle Scholar
  82. Naudon, L., Leroux-Nicollet, I. and Constentin, J. (1994) Short-term treatments with haloperidol or bromocryp-tine do not alter the density of the vesicular monoamine transporter.Neurosci. Lett. 173, 10.CrossRefGoogle Scholar
  83. O’Hearn, E.G., Battaglia, G., De Souza, E.B., Kuhar, M.J. and Molliver, M.E. (1988) Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: Immunocytochemical evidence for neurotoxicity.J. Neurosci. 8:2788–2803.PubMedGoogle Scholar
  84. Parrott, A.C. (1988) The psychobiology of MDMA or “Ecstasy”: symposium report.J. Psychopharmacol. 12, 97–102.CrossRefGoogle Scholar
  85. Parrott, A.C. and Lasky, J. (1998) Ecstasy (MDMA) effects upon mood and cognition: Before, during and after a Saturday night dance.Psychopharmacol 139(3), 261–268.Google Scholar
  86. Parrot, A.C, Lees, A., Granham, N.J., Jones, M. and Wesnes K. (1998) Cognitive performance in recreational users of MDMA or “Ecstasy”: evidence for memory deficits.J. Psychopharmacol. 12(1), 79–83.CrossRefGoogle Scholar
  87. Peroutka, S.J. (1987a) Incidence of recreational use of 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) on an undergraduate campus.N.E.J.M. 317, 1542–1543.Google Scholar
  88. Peroutka, S.J., Pascoe, N. and Faull, K.F. (1987b) Monoamine metabolites in the cerebrospinal fluid of recreational users of 3,4-methylenedioxymethamphetamine (MDMA; “Ecstasy”).Res. Comm. in Substance Abuse 8, 125–138.Google Scholar
  89. Post, R.M., Kotin, J., Goodwin, F.K. and Gordon, E.D. (1973) Psychomotor activity and cerebrospinal fluid amine metabolites in affective illness.Am. J. Psychiatry 130, 67–73.PubMedGoogle Scholar
  90. Post, R.M., Ballenger, J.C and Goodwin, F.K. (1980) Cerebrospinal fluid studies of neurotransmitter function in manic and depressive illness. In: Wood, J.H. (Ed)Neurobiology of Cerebrospinal Fluid, (New York, NY: Plenum Press), pp. 685–717.Google Scholar
  91. Price, L.H., Chamey, D.S. and Delgado, P.L., et al. (1990) Clinical studies of 5-HT function using I.V. L-Tryp-tophan.Prog. Neuro-Psychopharmacol. Biol. Psychiat.14, 459–472.Google Scholar
  92. Price, L.H., Ricaurte, G.A., Krystal, J. and Heninger, G. (1989) Neuroendocrine and mood responses to intravenous L-tryptophan in (+) 3,4-methylenedioxymethampheta-mine (MDMA) users,Arch. Gen. Psychiatry46, 20–22.Google Scholar
  93. Quattrone, A., Schettini, G., Annunziato, L. and Di Renzo, G. (1981) Pharmacological evidence of supersensitivity of central serotonergic receptors involved in the control of prolactin secretion.Eur. J. Pharmacol. 76, 9–13.PubMedCrossRefGoogle Scholar
  94. Ricaurte, G.A., Yuan, J. and McCann, U.D. (±) 3,4-Methylene-dioxymethamphetamine (MDMA, “Ecstasy”)-induced serotonin-neurotoxicity: Studies in animals.Neuropsy-chobiology, in press.Google Scholar
  95. Ricaurte, G.A., DeLanney, L.E., Irwin, I. and Langston, J.W. (1988a) Toxic effects of 3,4-methylenedioxymethamphet-amine on central serotonergic neurons in the primate: Importance of route and frequency of drug administration.Brain Res. 446: 165–168.PubMedCrossRefGoogle Scholar
  96. Ricaurte, G.A., Delanney, L.E., Wiener, S.G., Irwin, I. and Langston, J.W. (1988b) 5-Hydroxyindoleacetic acid in cerebrospinal fluid reflects serotonergic damage induced by 3,4-methylenedioxyrnethamphetamine in the CNS of non-human primates.Brain Res. 474, 359–363.PubMedCrossRefGoogle Scholar
  97. Ricaurte, G.A., Finnegan, K.T., Irwin, I. and Langston, J.W. (1990) Aminergic metabolites in cerebrospinal fluid of humans previously exposed to MDMA: preliminary observations.Ann. N. Y. Acad. Sci. 600, 699–710.PubMedCrossRefGoogle Scholar
  98. Ricaurte, G.A., Martello, A.L., Katz, J.L. and Martello, M.B. (1992) Lasting effects of (±)3,4-methylenedioxymetham-phetamine on central serotonergic neurons in non-human primates: Neurochemical observations.J. Pharmacol. Exp. Ther. 261, 616–622.PubMedGoogle Scholar
  99. Ricaurte, G.A., Sabol, K.E. and Seiden, L.S. (1994) Functional consequences of neurotoxic amphetamine exposure. In: Cho, A.K. and Segal, D.S. (Eds)Amphetamine and Its Analogs (San Diego, CA: Academic Press), pp. 297–313.Google Scholar
  100. Roy, A., Adinoff, B. and Linnoila, M. (1988) Acting out hostility in normal volunteers: negative correlation with levels of 5HIAA in cerebrospinal fluid.Psychiatry Res. 24, 187–194.PubMedCrossRefGoogle Scholar
  101. Saunders, N. and Wright, M.A. (1995) Ecstasy and the Dance Culture, (Exeter, Eng: BPC Wheatons).Google Scholar
  102. Scanzello, C.R., Hatzidimitriou, G., Martello, A.L., Katz, J.L. and Ricaurte, G.A. (1993) Serotonergic recovery after (±)3,4-(Methylenedioxy) methamphetamine injury: Observations in rats.J. Pharmacol. Exp. Ther. 264, 1484–1491.PubMedGoogle Scholar
  103. Scheffel, U., Szabo, Z., Mathews, W.B., Finlet, P.A., Dannals, R.F., Ravert, H.T., Szabo, K., Yuan, J. and Ricaurte, G.A. (1998) In vivo detection of short and long-term MDMA neurotoxicity: a positron emission tomography study in the living baboon brain.Synapse 29, 183–192.PubMedCrossRefGoogle Scholar
  104. Schmidt, C.J. (1987) Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine.J. Pharmacol. Exp. Ther. 240, 1–7.PubMedGoogle Scholar
  105. Schmidt, C.J., Wu, L. and Lovenberg, W. (1986) Methylenedioxymethamphetamine: a potentially neurotoxic amphetamine analog,Eur. J. Pharmacol.124, 175–178.Google Scholar
  106. Schneider, G.E. (1973) Early lesions of the superior colliculus: Factors affecting the formation of abnormal retinal projections.Brain Behav. Evol. 8, 73–109.PubMedCrossRefGoogle Scholar
  107. Semple, D., Ebmeier, K., Glabus, M., O’Carrol, R., Johnstone, E. (1999) Reduced in vivo binding to the serotonin transporter in the cerebral cortex of MDMA (“Ecstasy”) users.J British. Psychiatry 175:63–69.CrossRefGoogle Scholar
  108. Shulgin, A.T. and Nichols, D.E. (1978) Characterization of three new psychotomimetics. In: Stillman, R. and Wil-lette, R. (Eds),The Psychopharmacology of Hallucinogens (New York, NY: Pergamon Press), pp. 74–83.Google Scholar
  109. Stone, D.M., Hanson, G.L. and Gibb, J.W. (1987) Differences in the central serotonergic effects of 3,4-methylenedioxymethamphetamine (MDMA) in mice and rats.Neu-ropharmacol 26, 1657–1661.Google Scholar
  110. Stone, D.M., Stahl, D.C., Hanson, G.R. & Gibb, J.W. (1986) The effects of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) on monoaminergic systems in the rat brain.Eur. J. Pharmacol. 128, 41–48.PubMedCrossRefGoogle Scholar
  111. Sunderland, T., Tariot, P.N., Cohen, R.M., Newhouse, P.A., Mellow, A.M. and Mueller, E.A. (1987) Dose-dependent effects of deprenyl on CSF monoamine metabolites in patients with Alzheimer’s disease.Psychopharmacology 91, 293–296.PubMedCrossRefGoogle Scholar
  112. Tellegen A. Multidimensional Personality Questionaire. (1982) Copyright by Auke Tellegen.Google Scholar
  113. Vander Borght, T., Sima, A., Kilbourn, M.R., Desmond, T., Kuhl, D. and Frey, K. (1995) The vesicular monoamine transporter is not regulated by dopaminergic drug treatments.Eur. J. Pharmacol. 294, 577–583.PubMedCrossRefGoogle Scholar
  114. van Praag, H.M. (1986) (Auto) aggression and CSF 5-H1AA in depression and schizophrenia.Psychopharmacol Bulletin 22, 669–673.Google Scholar
  115. Virkkunen, M., Nautila, A., Goodwin, F.K. and Linnoila, M. (1987) Cerebrospinal fluid metabolite levels in male arsonists.Arch. Gen. Psychiatry 44, 241–247.PubMedGoogle Scholar
  116. Williams, H.L., Lester, B.K. and Coulter, J.D. (1969) Monoamines and the EEG stages of sleep.Acta Nerv. Super. 11, 188–192.Google Scholar
  117. Wilson, M.A., Ricaurte, G.A. and Molliver, M.E. (1989) Distinct morphologic classes of serotonergic axons in primates exhibit differential vulnerability to the psychotropic drug 3,4-methylenedioxymethampheta-mine.Neuroscience 28, 121–137.PubMedCrossRefGoogle Scholar
  118. Zohar, J., Mueller, E.A., Insel, T.R., Zohar-Kadouch, R.C. and Murphy, D.L. (1987) Serotonergic responsivity in obsessive-compulsive disorder: comparison of patients and healthy controls.Arch. Gen. Psychiatry 44, 946–951.PubMedGoogle Scholar
  119. Zuckerman, M., Eysenck, S. and Eysenck, H.J. (1978). Sensation seeking in England and America: Cross-cultural, age and sex comparisons.J. Consulting and Clin. Psychology 46(1), 139–149.CrossRefGoogle Scholar

Copyright information

© Springer 2001

Authors and Affiliations

  • George A. Ricaurte
    • 1
  • Una D. McCann
    • 2
  1. 1.Department of NeurologyJohns Hopkins Medical InstitutionsBaltimore
  2. 2.Department of Psychiatry Behavioral SciencesJohns Hopkins Medical InstitutionsBaltimore

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