The ugly side of amphetamines: Short-and long-term toxicity of 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy'), methamphetamine and d-amphetamine

Biological Chemistry

Volumn 392, Issue 1-2, 2011, Pages 103-115

  Steinkellner, Thomas ^a   Freissmuth, Michael ^a   Sitte, Harald H ^a   Montgomery, Therese ^a,b  

^a MEDICAL UNIVERSITY OF VIENNA   (Austria)

^b UNIVERSITY COLLEGE DUBLIN   (Ireland)

Author keywords

3,4 methylenedioxymethamphetamine (MDMA); addiction; amphetamine; disease

Indexed keywords

3,4 METHYLENEDIOXYMETHAMPHETAMINE; 5 HYDROXYINDOLEACETIC ACID; DEXAMPHETAMINE; METHAMPHETAMINE;

COGNITIVE DEFECT; DEATH; DEGENERATIVE DISEASE; DOPAMINERGIC NERVE CELL; DRUG ABUSE; DRUG DEPENDENCE; DRUG EFFECT; DRUG FATALITY; DRUG INTOXICATION; DRUG MECHANISM; DRUG PURITY; DRUG STRUCTURE; DRUG USE; HEART MUSCLE INJURY; HUMAN; MENTAL DISEASE; MULTIPLE DRUG ABUSE; NEUROTOXICITY; NONHUMAN; OXIDATIVE STRESS; PATHOGENESIS; PRIORITY JOURNAL; REVIEW;

AMPHETAMINES; ANIMALS; DEXTROAMPHETAMINE; HUMANS; METHAMPHETAMINE; MITOCHONDRIA; MOLECULAR STRUCTURE; N-METHYL-3,4-METHYLENEDIOXYAMPHETAMINE; PSYCHOSES, SUBSTANCE-INDUCED; SUBSTANCE-RELATED DISORDERS; TIME FACTORS;

ANIMALIA;

EID: 78651366871     PISSN: 14316730     EISSN: 14374315     Source Type: Journal    
DOI: 10.1515/BC.2011.016     Document Type: Review

References (176)

1. Abi-Dargham, A., van de Giessen, E., Slifstein, M., Kegeles, L.S., and Laruelle, M. (2009). Baseline and amphetamine-stimulated dopamine activity are related in drug-naive schizophrenic sub-jects. Biol. Psychiatry 65, 1091-1093.
2. Akil, M., Pierri, J.N., Whitehead, R.E., Edgar, C.L., Mohila, C., Sampson, A.R., and Lewis, D.A. (1999). Lamina-specific alter-ations in the dopamine innervation of the prefrontal cortex in schizophrenic subjects. Am. J. Psychiatry 156, 1580-1589.
3. Alves, E., Summavielle, T., Alves, CJ., Gomes-da-Silva, J., Barata, J.C., Fernandes, E., Bastos, Mde. L., Tavares, M.A., and Car-valho, F. (2007). Monoamine oxidase-B mediates ecstasy-induced neurotoxic effects to adolescent rat brain mitochondria. J. Neurosci. 27, 10203-10210.
4. Alves, E., Binienda, Z., Carvalho, F., Alves, CJ., Fernandes, E., de Lourdes, Bastos, M., Tavares, M.A., and Summavielle, T. (2009a). Acetyl-L-carnitine provides effective in vivo neuropro-tection over 3,4-methylenedioximethamphetamine-induced mitochondrial neurotoxicity in the adolescent rat brain. Neuro-science 158, 514-523.
5. Alves, E., Summavielle, T., Alves, CJ., Custodio, J.B., Fernandes, E., de Lourdes Bastos, M., Tavares, M.A., and Carvalho, F. (2009b). Ecstasy-induced oxidative stress to adolescent rat brain mitochondria in vivo: influence of monoamine oxidase type A. Addict. Biol. 15, 185-193.
6. Anderson, K.L. and Itzhak, Y. (2006). Methamphetamine-induced selective dopaminergic neurotoxicity is accompanied by an increase in striatal nitrate in the mouse. Ann. N.Y. Acad. Sci. 1074, 225-233.
7. Bankson, M.G. and Yamamoto, B.K. (2004). Serotonin-GABA interactions modulate MDMA-induced mesolimbic dopamine release. J. Neurochem. 91, 852-859.
8. 3H]paroxetine- labeled serotoninuptake sites. J. Pharmacol. Exp. Ther. 242, 911-916.
9. Baumann, M.H. and Rothman, R.B. (2009). Neural and cardial tox-icities associated with 3,4-methylenedioxymethamphetamine (MDMA). Int. Rev. Neurobiol. 88, 257-296.
10. Baumann, M.H., Wang, X., and Rothman, R.B. (2007). 3,4-Methy- lenedioxymethamphetamine (MDMA) neurotoxicity in rats, a reappraisal of past and present findings. Psychopharmacology 189, 407-424.
11. Baumann, M.H., Clark, R.D., Franken, F.H., Rutter, JJ., and Roth-man, R.B. (2008). Tolerance to 3,4-methylenedioxymethamphe-tamine in rats exposed to single high-dose binges. Neuroscience 152, 773-784.
12. Baylen, C.A. and Rosenberg, H. (2006). A review of the acute sub-jective effects of MDMA/ecstasy Addiction 101, 933-947.
13. Beardsley, P.M., Balster, R.L., and Harris, L.S. (1986). Self-admin-istration of methylenedioxymethamphetamine (MDMA) by rhe-sus monkeys. Drug Alcohol Depend. 18, 149-157.
14. Bedi, G., Van Dam, N.T., and Redman, J. (2010). Ecstasy (MDMA) and high prevalence psychiatric symptomatology, somatic anxi-ety symptoms are associated with polydrug, not ecstasy, use. J. Psychopharmacol. 24, 233-240.
15. Berman, S.M., Kuczenski, R., McCracken, J.T., and London, E.D. (2009). Potential adverse effects of amphetamine treatment on brain and behaviour: a review. Mol. Psychiatry 14, 123-142.
16. Boenisch, H. and Bruess, M. (2006). The norepinephrine transporter in physiology and disease. In: Handbook of Experimental Pharmacology, Vol. 175, H.H. Sitte and M. Freissmuth, eds. (Heidelberg: Springer Verlag), pp. 485-524.
17. Brown, J.M. and Yamamoto, B.K. (2003). Effects ofamphetamines on mitochondrial function, role of free radicals and oxidative stress. Pharmacol. Ther. 99, 45-53.
18. Bruno, R., Matthews, A.J., Topp, L., Degenhardt, L., Gomez, R., and Dunn, M. (2009). Can the severity of dependence scale be usefully applied to 'ecstasy'? Neuropsychobiology 60, 137-147.
19. Buckholtz, J.W., Treadway, M.T., Cowan, R.L., Woodward, N.D., Benning, S.D., Li, R., Ansari, M.S., Baldwin, R.M., Schwartz-man, A.N., Shelby, E.S., et al. (2010). Mesolimbic dopamine reward system hypersensitivity in individuals with psychopathic traits. Nat Neurosci. 13, 419-421.
20. Budygin, E.A., Brodie, M.S., Sotnikova, T.D., Mateo, Y., John, C.E., Cyr, M., Gainetdinov, R.R., and Jones, S.R. (2004). Dis-sociation of rewarding and dopamine transporter-mediated prop-erties ofamphetamine. Proc. Natl. Acad. Sci. USA 101, 7781-7786.
21. Busceti, C.L., Biagioni, F., Riozzi, B., Battaglia, G., Storto, M., Cinque, C., Molinaro, G., Gradini, R., Caricasole, A., Canudas, A.M., et al. (2008). Enhanced tau phosphorylation in the hip-pocampus of mice treated with 3,4-methylenedioxymethamphet-amine ('Ecstasy'). J. Neurosci. 28, 3234-3245.
22. Capela, J.P., Carmo, H., Remiao, F., Bastos, M.L., Meisel, A., and Carvalho, F. (2009). Molecular and cellular mechanisms of ecstasy-induced neurotoxicity, an overview. Mol. Neurobiol. 39, 210-271.
23. Caspi, A., Sugden, K., Moffitt, T.E., Taylor, A., Craig, I.W., Har-rington, H., McClay, J., Mill, J., Martin, J., Braithwaite, A., et al. (2003). Influence of life stress on depression, moderation by a polymorphism in the 5-HTT gene. Science 301, 386-389.
24. Chang, L., Alicata, D., Ernst, T., and Volkow, N. (2007). Structural and metabolic brain changes in the striatum associated with methamphetamine abuse. Addiction 1, 16-32.
25. Chen, R., Furman, C.A., Zhang, M., Kim, M.N., Gereau, R.W., 4th, Leitges, M., and Gnegy, M.E. (2009). Protein kinase Cβ is a critical regulator of dopamine transporter trafficking and regulates the behavioral response to amphetamine in mice. J. Pharmacol. Exp. Ther. 328, 912-920.
26. Chipana, C., Torres, I., Camarasa, J., Pubill, D., and Escubedo, E. (2008). Memantine protects against amphetamine derivativesinduced neurotoxic damages in rodents. Neuropharmacology 54, 1254-1263.
27. Clemens, K.J., Cornish, J.L., Hunt, G.E., and McGregor, I.S. (2006). Intravenous methamphetamine self-administration in rats, effects of intravenous or intraperitoneal MDMA co-administration. Pharmacol. Biochem. Behav. 85, 454-463.
28. Colussi-Mas, J. and 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, 1895-1910.
29. Cruickshank, C.C. and Dyer, K.R. (2009). A review of the clinical pharmacology ofmethamphetamine. Addiction 104, 1084-1099.
30. Curran, H.V. (2000). Is MDMA ('Ecstasy') neurotoxic in humans? An overview of evidence and of methodological problems in research. Neuropsychobiology 42, 34-41.
31. Davidson, C., Gow, A.J., Lee, T.H., and Ellinwood, E.H. (2001). Methamphetamine neurotoxicity: necrotic and apoptotic mechanisms and relevance to human abuse and treatment. Brain Res. Brain Res. Rev. 36, 1-22.
32. de la Torre, R. and Farre, M. (2004). Neurotoxicity of MDMA (ecstasy), the limitations of scaling from animals to humans. Trends Pharmacol. Sci. 25, 505-508.
33. de la Torre, R., Farre, M., Roset, P.N., Lopez, C.H., Mas, M., Ortuno, J., Menoyo, E., Pizarro, N., Segura, J., and Cami, J. (2000). Pharmacology of MDMA in humans. Ann. N.Y Acad. Sci. 914, 225-237.
34. Degenhardt, L., Bruno, R., and Topp, L. (2010). Is ecstasy a drug of dependence? Drug Alcohol Depend. 107, 1-10.
35. Di Giovanni, G., Di Matteo, V, and Esposito, E. (2002). Serotonin/dopamine interaction-focus on 5-HT2C receptor, a new target of psychotropic drugs. Indian J. Exp. Biol. 40, 1344-1352.
36. Di Matteo, V, Di Giovanni, G., Pierucci, M., and Esposito, E. (2008). Serotonin control of central dopaminergic function, focus on in vivo microdialysis studies. Prog. Brain Res. 172, 7-44.
37. Diller, A.J., Rocha, A., Cardon, A.L., Valles, R., Wellman, P.J., and Nation, J.R. (2007). The effects of concurrent administration of +/-3,4-methylenedioxymethamphetamine and cocaine on conditioned place preference in the adult male rat. Pharmacol. Biochem. Behav. 88, 165-170.
38. Docherty, J.R. (2008). Pharmacology of stimulants prohibited by the world anti-doping agency (WADA). Br. J. Pharmacol. 154, 606-622.
39. Durdle, H., Lundahl, L.H., Johanson, C.E., and Tancer, M. (2008). Major depression, the relative contribution of gender, MDMA, and cannabis use. Depress Anxiety 25, 241-247.
40. EMCDDA. (2009). Annual statistical report on state of drugs problem in Europe. European Monitoring Centre for Drugs and Drug Addiction. Luxembourg: Publications Office of the European Union, 2009.
41. Escobedo, I., O'Shea, E., Orio, L., Sanchez, V, Segura, M., de la Torre, R., Farre, M., Green, A.R., and Colado, M.I. (2005). A comparative study on the acute and long-term effects of MDMA and 3,4-dihydroxymethamphetamine (HHMA) on brain mono-amine levels after i.p. or striatal administration in mice. Br. J. Pharmacol. 144, 231-241.
42. Esteban, B., O'Shea, E., Camarero, J., Sanchez, V, Green, A.R., and Colado, M.I. (2001). 3,4-Methylenedioxymethamphetamine induces monoamine release, but not toxicity, when administered centrally at a concentration occuring following a peripherally injected neurotoxic dose. Psychopharmacology 154, 251-260.
43. Falk, E.M., Cook, V.J., Nichols, D.E., and Sprague, J.E. (2002). An antisense oligonucleotide targeted at MAO-B attenuates rat stria-tal serotonergic neurotoxicity induced by MDMA. Pharmacol. Biochem. Behav. 72, 617-622.
44. Fantegrossi, W.E. (2007). Reinforcing effects of methylenedioxy amphetamine congeners in rhesus monkey: are intravenous self-administration experiments relevant to MDMA neurotoxicity? Psychopharmacology (Berlin) 189, 471-482.
45. Fantegrossi, W.E., Ullrich, T., Rice, K.C., Woods, J.H., and Winger, G. (2002). 3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') and its stereoisomers as reinforcers in rhesus monkeys, serotonergic involvement. Psychopharmacology 161, 356-364.
46. Farre, M., de la Torre, R., Mathina, B.O., Roset, P.N., Peiro, A.M., Torrens, M., Ortuno, J., Pujadas, M., and Cami, J. (2004). Repeated doses administration of MDMA in humans: pharma-cological effects and pharmacokinetics. Psychopharmacol. (Berl.). 173, 364-375.
47. Fischer C., Hatzidimitriou, G., Wlos, J., Katz, J., and Ricaurte, G. (1995). Reorganization of ascending 5-HT axon projections in animals previously exposed to the recreational drug (+/-) 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy'). J. Neu-rosci. 15, 5476-5485.
48. Fog, J.U., Khoshbouei, H., Holy, M., Owens, W.A., Vaegter, C.B., Sen, N., Nikandrova, Y., Bowton, E., McMahon, D.G., Colbran, RJ., et al. (2006). Calmodulin kinase II interacts with the dopa-mine transporter C terminus to regulate amphetamine-induced reverse transport. Neuron 51, 417-429.
49. Fornai, F., Giorgi, F.S., Gesi, M., Chen, K., Alessri, M.G., and Shi, J.C. (2001). Biochemical effects of the monoamine neurotoxins DSP-4 and MDMA in specific brain regions of MAO-B-defi-cient mice. Synapse 39, 213-221.
50. Forrest, L.R., Zhang, Y.W., Jacobs, M.T., Gesmonde, J., Xie, L., Honig, B.H., and Rudnick, G. (2008). Mechanism for alternating access in neurotransmitter transporters. Proc. Natl. Acad. Sci. USA 105, 10338-10343.
51. Gainetdinov, R.R., Mohn, A.R., and Caron, M.G. (2001). Genetic animal models, focus on schizophrenia. Trends Neurosci. 24, 527-533.
52. Gainetdinov, R.R., Sotnikova, T.D., and Caron, M.G. (2002). Mon-oamine transporter pharmacology and mutant mice. Trends Phar-macol. Sci. 23, 367-373.
53. Giorgi, F.S., Lazzeri, G., Natale, G., Iudice, A., Ruggieri, S., Papa-relli, A., Murri, L., and Fornai, F. (2006). MDMA and seizures, a dangerous liaison? Ann. N.Y. Acad. Sci. 1074, 357-364.
54. Giros, B., Jaber, M., Jones, S.R., Wightman, R.M., and Caron, M.G. (1996). Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature 379, 606-612.
55. Goodwin, J.S., Larson, G.A., Swant, J., Sen, N, Javitch, J.A., Zah-niser, N.R., De Felice, L.J., and Khoshbouei, H. (2009). Amphet-amine and methamphetamine differentially affect dopamine transporters in vitro and in vivo. J. Biol. Chem. 284, 2978-2989.
56. Gouzoulis-Mayfrank, E. and Daumann, J. (2006a). The confounding problem of polydrug use in recreational ecstasy/MDMA users: a brief overview. J. Psychopharmacol. 20, 188-193.
57. Gouzoulis-Mayfrank, E. and Daumann, J. (2006b). Neurotoxicity of methylenedioxyamphetamines (MDMA; ecstasy) in humans, how strong is the evidence for persistent brain damage? Addic-tion 101, 348-361.
58. Graham, D.L., Noailles, P.A., and Cadet, J.L. (2008). Differential neurochemical consequences of an escalating dose-binge regi-men followed by single-day multiple-dose methamphetamine challenges. J. Neurochem. 105, 1873-1885.
59. Granado, N, O'Shea, E., Bove, J., Vila, M., Colado, M.I., and Moratalla, R. (2008). Persistent MDMA-induced dopaminergic neurotoxicity in the striatum and substantia nigra of mice. J. Neurochem. 107, 1102-1112.
60. Granado, N., Ares-Santos, S., O'Shea, E., Vicario-Abejon, C., Cola-do, M.I., and Moratalla R. (2010). Selective vulnerability in striosomes and the nigrostriatal dopaminergic pathway after methamphetamine administration. Early loss of TH in striosomes after methamphetamine. Neurotox. Res. 18, 48-58.
61. Green, A.R., Mechan, A.O., Elliott, J.M., O'Shea, E., and Colado, M.I. (2003). The pharmacology and clinical pharmacology of3,4- methylenedioxymethamphetamine (MDMA, 'ecstasy'). Phar-macol. Rev. 55, 463-508.
62. Green, A.R., Gabrielsson, J., Marsden, C.A., and Fone, K.C. (2009). MDMA, on the translation from rodent to human dosing. Psy-chopharmacology 204, 375-378.
63. Gudelsky, G.A. and Nash, J.F. (1996). Carrier-mediated release of serotonin by 3,4-methylenedioxymethamphetamine: implica-tions for serotonin-dopamine interactions. J. Neurochem. 66, 243-249.
64. Gudelsky, G.A., Yamamoto, B.K., and Nash, J.F. (1994). Potentia-tion of 3,4-methylenedioxymethamphetamine-induced dopamine release and serotonin neurotoxicity by 5-HT2 receptor agonists. Eur. J. Pharmacol. 264, 325-330.
65. Guilarte, T.R. (2001). Is methamphetamine abuse a risk factor in parkinsonism? Neurotoxicology 22, 725-731.
66. Hall, A.P. and Henry, J.A. (2006). Acute toxic effects of 'Ecstasy' (MDMA) and related compounds, overview of pathophysiology and clinical management. Br. J. Anaesth. 96, 678-685.
67. Harvey, D.C., Lacan, G., and Melegan, W.P. (2000). Regional het-erogeneity of dopaminergic deficits in vervet monkey striatum and substantia nigra after methamphetamine exposure. Exp. Brain Res. 133, 349-358.
68. Hatzidimitriou, G., McCann, U.D., and Ricaurte, GA. (1999). Altered serotonin innervation patterns in the forebrain of mon-keys treated with (+/-)3,4-methylenedioxymethamphetamine seven years previously, factors influencing abnormal recovery J. Neurosci. 19, 5096-5107.
69. Hermens, D.F., Lubman, D.I., Ward, P.B., Naismith, S.L., and Hic-kie, I.B. (2009). Amphetamine psychosis: a model for studying the onset and course of psychosis. Med. J. Aust. 190, S22-S25.
70. Hewton, R., Salem, A., and Irvine R.J. (2007). Potentiation of3,4-methylenedioxymethamphetamine-induced 5-HT release in the rat substantia nigra by clorgyline, a monoamine oxidase A inhib-itor. Clin. Exp. Pharmacol. Physiol. 34, 1051-1057.
71. Hnasko, T.S., Sotak, B.N., and Palmiter, R.D. (2007). Cocaine-con-ditioned place preference by dopamine-deficient mice is medi-ated by serotonin. J. Neurosci. 27, 12484-12488.
72. Howell, L.L. and Kimmel, H.L. (2008) Monoamine transporters and psychostimulant addiction. Biochem. Pharmacol. 75, 196-217.
73. Hrometz, S.L., Brown, A.W., Nichols, D.E., and Sprague, J.E. (2004). 3,4-Methylenedioxymethamphetamine (MDMA, ecsta-sy)-mediated production of hydrogen peroxide in an in vitro model: the role of dopamine, the serotonin-reuptake transporter, and monoamine oxidase-B. Neurosci. Lett. 26, 56-59.
74. Itzhak, Y., Ali, S.F., Achat, C.N., and Anderson, K.L. (2003). Rel-evance of MDMA ('ecstasy')-induced neurotoxicity to long-last-ing psychomotor stimulation in mice. Psychopharmacology 166, 241-248.
75. Iwata, S.I., Hewlett, G.H., Ferrell, S.T., Kantor, L., and Gnegy, M.E. (1997). Enhanced dopamine release and phosphorylation of synapsin I and neuromodulin in striatal synaptosomes after repeated amphetamine. J. Pharmacol. Exp. Ther. 283, 1445-1452.
76. Jones, S.R., Gainetdinov, R.R., Wightman, R.M., and Caron, M.G. (1998). Mechanisms of amphetamine action revealed in mice lacking the dopamine transporter. J. Neurosci. 18, 1979-1986.
77. Jones, D.C., Duvauchelle, C., Ikegami, A., Olsen, C.M., Lau, S.S., de la Torre, R., and Monks, TJ. (2005). Serotonergic neurotoxic metabolites of ecstasy identified in rat brain. J. Pharmacol. Exp. Ther. 313, 422-431.
78. Jones, K., Brennan, K.A., Colussi-Mas, J., and Schenk, S. (2010). Tolerance to 3,4-methylenedioxymethamphetamine is associated with impaired serotonin release. Addict. Biol. 15, 289-298.
79. Kalivas, P.W. (2007). Cocaine and amphetamine-like psychostimu-lants, neurocircuitry and glutamate neuroplasticity Dialogues Clin. Neurosci. 9, 389-397.
80. Kalivas, P.W. and Volkow, N.D. (2005). The neural basis of addic-tion, a pathology of motivation and choice. Am. J. Psychiatry 162, 1403-1413.
81. Kalivas, P.W., Duffy, P., and White, S.R. (1998). MDMA elicits behavioral and neurochemical sensitization in rats. Neuropsy-chopharmacology 18, 469-479.
82. Kantor, L., Zhang, M., Guptaroy, B., Park, Y.H., and Gnegy, M.E. (2004). Repeated amphetamine couples norepinephrine trans-porter and calcium channel activities in PC12 cells. J. Pharma-col. Exp. Ther. 311, 1044-1051.
83. Karam, C.S., Ballon, J.S., Bivens, N.M., Freyberg, Z., Girgis, R.R., Lizardi-Ortiz, J.E., Markx, S., Lieberman, J.A., and Javitch J.A. (2010). Signaling pathways in schizophrenia: emerging targets and therapeutic strategies. Trends Pharmacol. Sci. 31, 381-390.
84. Karila, L., Weinstein, A., Aubin, HJ., Benyamina, A., Reynaud, M., and Batki, S.L. (2010). Pharmacological approaches to meth-amphetamine dependence: a focused review. Br. J. Clin. Phar-macol. 69, 578-592.
85. Karlsen, S.N., Spigset, O., and Slordal, L. (2008). The dark side of ecstasy, neuropsychiatric symptoms after exposure to 3,4-methy- lenedioxymethamphetamine. Basic Clin. Pharmacol. Toxicol. 102, 15-24.
86. Kauer, J.A. and Malenka, R.C. (2007). Synaptic plasticity and addiction. Nat. Rev. Neurosci. 8, 844-858.
87. Kish, S., Fitzmaurice, P., Chang, L., Furukawa, Y., and Tong, J. (2010a). Low striatal serotonin transporter protein in a human polydrug MDMA (ecstasy) user, a case study. J. Psychophar-macol. 24, 281-284.
88. 11C]DASB and structural brain imaging study. Brain 133, 1779-1797.
89. Koch, S. and Galloway, M.P. (1997). MDMA induced dopamine release in vivo: role of endogenous serotonin. J. Neural Transm. 104, 135-146.
90. Kolbrich, E.A., Goodwin, R.S., Gorelick, D.A., Hayes, RJ., Stein, E.A., and Huestis, M.A. (2008). Plasma pharmacokinetics of 3,4- methylenedioxymethamphetamine after controlled oral administration to young adults. Ther. Drug Monit. 30, 320-332.
91. Krasnova, I.N. and Cadet, J.L. (2009). Methamphetamine toxicity and messengers of death. Brain Res. Rev. 60, 379-407.
92. Kuypers, K.P. and Ramaekers, J.G. (2007). Acute dose of MDMA (75 mg) impairs spatial memory for location but leaves contex-tual processing of visuospatial information unaffected. Psycho-pharmacology (Berlin) 189, 557-563.
93. Leonardi, E.T. and Azmitia, E.C. (1994). MDMA (ecstasy) inhibi-tion of MAO type A and type B, comparisons with fenfluramine and fluoxetine (Prozac). Neuropsychopharmacology 10, 231-238.
94. Li, S.X., Li, J., Wang, X., Peng, Z.G., Kuang, W.H., and Huang, M.S. (2006). Long-term neurotoxic effects of MDMA results in cortical and hippocampal structural changes. Sheng Li Xue Bao 58, 34-40.
95. Licata, S.C., Schmidt, H.D., and Pierce, R.C. (2004). Suppressing calcium/calmodulin-dependent protein kinase II activity in the ventral tegmental area enhances the acute behavioural response to cocaine but attenuates the initiation of cocaine-induced beha-vioural sensitization in rats. Eur. J. Neurosci. 19, 405-414.
96. Lile, J.A., Ross, J.T., and Nader, M.A. (2005). A comparison of the reinforcing efficacy of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') with cocaine in rhesus monkeys. Drug Alco-hol Depend. 78, 135-140.
97. 2+/calmo-dulin-dependent protein kinase II in the nucleus accumbens shell enhances behavioral responding to amphetamine. J. Neurosci. 30, 939-949.
98. Lyles, J. and Cadet, J.L. (2003). Methylenedioxymethamphetamine (MDMA, Ecstasy) neurotoxicity, cellular and molecular mech-anisms. Brain Res. Brain Res. Rev. 42, 155-168.
99. Mart́in-Santos, R., Torrens, M., Poudevida, S., Langohr, K., Cuyas, E., Pacifici R., Farre, M., Pichini, S., and de la Torre, R. (2010). 5-HTTLPR polymorphism, mood disorders and MDMA use in a 3-year follow-up study. Addict. Biol. 15, 15-22.
100. McCambridge, J., Mitcheson, L., Winstock, A., and Hunt, N. (2005). Five-year trends in patterns of drug use among people who use stimulants in dance contexts in the United Kingdom. Addiction 100, 1140-1149.
101. McCann, U.D., Ridenour, A., Shaham, Y., and Ricaurte, GA. (1994). Serotonin neurotoxicity after (+/-)3,4-methylenedioxy-methamphetamine (MDMA; 'Ecstasy'), a controlled study in humans. Neuropsychopharmacology 10, 129-138.
102. 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.
103. McCann, U.D., Mertl, M., Eligulashvili, V, and Ricaurte, GA. (1999). Cognitive performance in (+/-)3,4-methylenedioxyme-thamphetamine (MDMA, 'ecstasy') users, a controlled study. Psychopharmacology 143, 417-425.
104. McCann, U.D., Szabo, Z., Vranesic, M., Palermo, M., Mathews, W.B., Ravert, H.T., Dannals, R.F., and Ricaurte, G.A. (2008). Positron emission tomographic studies of brain dopamine and serotonin transporters in abstinent (+/-)3,4-methylenedioxy-methamphetamine ('ecstasy') users, relationship to cognitive performance. Psychopharmacology 200, 439-450.
105. McClung, J., Fantegrossi, W., and Howell, L.L. (2010). Reinstate-ment of extinguished amphetamine self-administration by 3,4- methylenedioxymethamphetamine (MDMA) and its enantiomers in rhesus monkeys. Psychopharmacology 210, 75-83.
106. Melega, W.P., Jorgensen, M.J., Lacan, G., Way, B.M., Pham, J., Morton, G., Cho, A.K., and Fairbanks, L.A. (2008). Long-term methamphetamine administration in the vervet monkey models aspects of a human exposure: brain neurotoxicity and behavioral profiles. Neuropsychopharmacology 33, 1441-1452.
107. Modi, G.M., Yang, P.B., Swann, A.C., and Dafny, N. (2006). Chron-ic exposure to MDMA (Ecstasy) elicits behavioral sensitization in rats but fails to induce cross-sensitization to other psycho-stimulants. Behav. Brain Funct. 2, 1.
108. Monks, TJ., Jones, D.C., Bai, F., and Lau, S.S. (2004). The role of metabolism in 3,4-(+)-methylenedioxyamphetamine and 3,4-(+)- methylenedioxymethamphetamine (ecstasy) toxicity Ther. Drug Monit. 26, 132-136.
109. Moon, K.H., Upreti, V.V., Yu, L.R., Lee, I.J., Ye, X., Eddington, N.D., Veenstra, T.D., and Song, BJ. (2008). Mechanism of3,4- methylenedioxymethamphetamine (MDMA, ecstasy)-mediated mitochondrial dysfunction in rat liver. Proteomics 8, 3906-3918.
110. Morton, J. (2005). Ecstasy, pharmacology and neurotoxicity Curr. Opin. Pharmacol. 5, 79-86.
111. Nash, J.F., Meltzer, H.Y., and Gudelsky, G.A. (1990). Effect of3,4-methylenedioxymethamphetamine on 3,4-dihydroxyphenylala-nine accumulation in the striatum and nucleus accumbens. J. Neurochem. 54, 1062-1067.
112. Nestler, EJ. (2005). Is there a common molecular pathway for addiction? Nat. Neurosci. 8, 1445-1449.
113. Parrott, A.C. (2006). MDMA in humans, factors which affect the neuropsychobiological profiles of recreational ecstasy users, the integrative role of bioenergetic stress. J. Psychopharmacol. 20, 147-163.
114. Partilla, J.S., Dempsey, A.G., Nagpal, A.S., Blough, B.E., Baumann, M.H., and Rothman, R.B. (2006). Interaction of amphetamines and related compounds at the vesicular monoamine transporter. J. Pharmacol. Exp. Ther. 319, 237-246.
115. Paulson, P.E. and Robinson, T.E. (1995). Amphetamine-induced time-dependent sensitization of dopamine neurotransmission in the dorsal and ventral striatum, a microdialysis study in behaving rats. Synapse 19, 56-65.
116. Peleg-Raibstein, D., Yee, B.K., Feldon, J., and Hauser, J. (2009). The amphetamine sensitization model of schizophrenia, rele-vance beyond psychotic symptoms? Psychopharmacology 4, 603-621.
117. Peraile, I., Torres, E., Mayado, A., Izco, M., Lopez-Jimenez, A., Lopez-Moreno, J.A., Colado, M.I., and O'Shea, E. (2010). Dopamine transporter down-regulation following repeated cocaine, implications for 3,4-methylenedioxymethamphetamine-induced acute effects and long-term neurotoxicity in mice. Br. J. Pharmacol. 159, 201-211.
118. Pierce, R.C. and Kalivas, R.W. (1997). A circuitry model of the expression ofbehavioural sensitization to amphetamine-like psy-chostimulants. Brain Res. Brain Res. Rev. 25, 192-216.
119. Pierce, R.C., Quick, E.A., Reeder, D.C., Morgan, Z.R., and Kalivas, P.W. (1998). Calcium-mediated second messengers modulate the expression of behavioral sensitization to cocaine. J. Pharmacol. Exp. Ther. 286, 1171-1176.
120. Pirona, A. and Morgan, MJ. (2010). An investigation of the suba-cute effects of ecstasy on neuropsychological performance, sleep and mood in regular ecstasy users. J. Psychopharmacol. 24, 175-185.
121. Pourahmad, J., Eskandari, M.R., Nosrati, M., Kobarfard, F., and Khajeamiri, A.R. (2010). Involvement of mitochondrial/lysoso-mal toxic cross-talk in ecstasy induced liver toxicity under hyperthermic condition. Eur. J. Pharmacol. 643, 162-169.
122. Pubill, D., Canudas, A.M., Pallas, M., Camins, A., Camarasa, J., and Escubedo, E. (2003). Differential glial response to meth-amphetamine-and methylendioxymethamphetamine-induced neurotoxicity Naunyn-Schmiedebergs Arch. Pharmacol. 367, 490-499.
123. Puerta, E., Hervias, I., Goni-Allo, B., Zhang, S.F., Jordan, J., Starkov, A.A., and Aguirre, N. (2010). Methylenedioxymethamphe-tamine inhibits mitochondrial complex I activity in mice: a possible mechanism underlying neurotoxicity Br. J. Pharmacol. 160, 233-245.
124. Quinton, M.S. and Yamamoto, B.K. (2006). Causes and conse-quences of methamphetamine and MDMA toxicity AAPS J. 8, E337-E347.
125. Ramos, M., Goni-Allo, B., and Aguirre, N. (2005). 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 30, 2180-2191.
126. Ratzenboeck, E., Saria, A., Kriechbaum, N., and Zernig, G. (2001). Reinforcing effects of MDMA ('ecstasy') in drug-naive and cocaine-trained rats. Pharmacology 62, 138-144.
127. Reneman, L., Lavalaye, J., Schmand, B., de Wolff, F.A., van den Brink, W., den Heeten, GJ., and Booij, J. (2001). Cortical sero-tonin transporter density and verbal memory in individuals who stopped using 3,4- methylenedioxymethamphetamine (MDMA or 'ecstasy'): preliminary findings. Arch. Gen. Psychiatry 58, 901-906.
128. Rezin, G.T., Amboni, G., Zugno, A.I., Quevedo, J., and Streck, E.L. (2009). Mitochondrial dysfunction and psychiatric disorders. Neurochem. Res. 34, 1021-1029.
129. Ricaurte, G.A. and McCann, U.D. (2001). Assessing long-term effects of MDMA (Ecstasy). Lancet 358, 1831-1832.
130. Ricaurte, G.A., Forno, L.S., Wilson, M.A., DeLanney, L.E., Irwin, I., Molliver, M.E., and Langston J.W. (1988). (+/-)3,4-Methy- lenedioxymethamphetamine selectively damages central seroto-nergic neurons in nonhuman primates. J. Am. Med. Assoc. 260, 51-55.
131. Ricaurte, G.A., Mechan, A.O., Yuan, J., Hatzidimitriou, G., Xie, T., Mayne, A.H., and McCann, U.D. (2005). Amphetamine treat-ment similar to that used in the treatment of adult attention-deficit/hyperactivity disorder damages dopaminergic nerve endings in the striatum of adult nonhuman primates. J. Phar-macol. Exp. Ther. 315, 91-98.
132. Robledo, P., Balerio, G., Berrendero, F., and Maldonado, R. (2004a). Study of the behavioural responses related to the potential addic-tive properties of MDMA in mice. Naunyn-Schmiedebergs Arch. Pharmacol. 369, 338-349.
133. Robledo, P., Mendizabal, V., Ortuno, J., de la Torre, R., Kieffer, B.L., and Maldonado, R. (2004b). The rewarding properties of MDMA are preserved in mice lacking mu-opioid receptors. Eur. J. Neurosci. 20, 853-858.
134. Roiser, J.P., Cook, LJ., Cooper, J.D., Rubinsztein, D.C., and Saha-kian, B.J. (2005). Association of a functional polymorphism in the serotonin transporter gene with abnormal emotional process-ing in ecstasy users. Am. J. Psychiatry 162, 609-612.
135. Saier, M.H. Jr. (2000). A functional-phylogenetic classification sys-tem for transmembrane solute transporters. Microbiol. Mol. Biol. Rev. 64, 354-411.
136. Salahpour, A., Ramsey, AJ., Medvedev, I.O., Kile, B., Sotnikova, T.D., Holmstrand, E., Ghisi, V, Nicholls, PJ., Wong, L., Murphy, K., et al. (2008). Increased amphetamine-induced hyperactivity and reward in mice overexpressing the dopamine transporter. Proc. Natl. Acad. Sci. USA 105, 4405-4410.
137. Schenk, S. (2009). MDMA self-administration in laboratory ani-mals, a summary of the literature and proposal for future research. Neuropsychobiology 60, 130-136.
138. Schenk, S., Hely, L., Gittings, D., Lake, B., and Daniela, E. (2008). Effects of priming injections of MDMA and cocaine on rein statement of MDMA-and cocaine-seeking in rats. Drug Alcohol Depend. 96, 249-255.
139. Schifano, F. (2000). Potential human neurotoxicity of MDMA ('Ecstasy'), subjective self-reports, evidence from an Italian drug addiction centre and clinical case studies. Neuropsychobiology 42, 25-33.
140. Schmidt, CJ. (1987). Neurotoxicity of the psychedelic ampheta-mine, methylenedioxymethamphetamine. J. Pharmacol. Exp. Ther. 240, 1-7.
141. Schmidt, CJ., Wu, L., and Lovenberg, W. (1986). Methylenedioxy- methamphetamine, a potentially neurotoxic amphetamine ana-logue. Eur. J. Pharmacol. 124, 175-178.
142. Schmidt, C.J., Sullivan, C.K., and Fadayel, G.M. (1994). Blockade of striatal 5-hydroxytryptamine2 receptors reduces the increase in extracellular concentrations of dopamine produced by the amphetamine analogue 3,4-methylenedioxymethamphetamine. J. Neurochem. 62, 1382-1389.
143. Schmued, L.C. (2003). Demonstration and localization of neuronal degeneration in the rat forebrain following a single exposure to MDMA. Brain Res. 974, 127-133.
144. Scott, R.M., Hides, L., Allen, J.S., Burke, R., and Lubman, D.I. (2010). Depressive and anxiety symptomatology in ecstasy users, the relative contribution of genes, trauma, life stress and drug use. Psychopharmacology 209, 25-36.
145. Seeman, P. and Niznik, H.B. (1990). Dopamine receptors and trans-porters in Parkinson's disease and schizophrenia. FASEB J. 4, 2737-2744.
146. Segal, D.S. and Kuczenski, R. (1987). Individual differences in responsiveness to single and repeated amphetamine administra-tion: behavioral characteristics and neurochemical correlates. J. Pharmacol. Exp. Ther. 242, 917-926.
147. Semple, D.M., Ebmeier, K.P., Glabus, M.F., O'Carroll, R.E., and Johnstone, E.C. (1999). Reduced in vivo binding to the serotonin transporter in the cerebral cortex of MDMA ('ecstasy') users. Br. J. Psychiatry 175, 63-69.
148. + and substrate is triggered by substrate in a second binding site. Mol. Cell 30, 667-677.
149. Shin, R., Qin, M., Liu, Z.H., and Ikemoto, S. (2008). Intracranial self-administration of MDMA into the ventral striatum of the rat, differential roles of the nucleus accumbens shell, core, and olfactory tubercle. Psychopharmacology 198, 261-270.
150. Singer, B.F., Loweth, J.A., Neve, R.L., and Vezina, P. (2010). Tran-sient viral-mediated overexpression of α-calcium/calmodulin-dependent protein kinase II in the nucleus accumbens shell leads to long-lasting functional upregulation of α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors: dopamine type-1 receptor and protein kinase A dependence. Eur. J. Neurosci. 31, 1243-1251.
151. --coupled neurotransmitter transporters-why ampheta-mines take two to tango. J. Neurochem. 112, 340-355.
152. Soar, K., Parrott, A., and Turner, J. (2009). Attributions for psycho-biological changes in ecstasy/MDMA and other polydrug users. J. Psychopharmacol. 23, 745-758.
153. Song, B.J., Moon, K.H., Upretti, V.V., Eddington, N.D., and Lee, I.J. (2010). Mechanisms of MDMA (ecstasy)-induced oxidative stress, mitochondrial dysfunction and organ damage. Curr. Pharm. Biotechnol. 11, 434-443.
154. Sonsalla, P.K., Jochnowitz, N.D., Zeevalk, G.D., Oostveen, J.A., and Hall, E.D. (1996). Treatment of mice with methamphetamine produces cell loss in the substantia nigra. Brain Res. 738, 172-175.
155. Sora, I., Li, B., Igari, M., Hall, F.S., and Ikeda, K. (2010). Trans-genic mice in the study of drug addiction and the effects of psychostimulant drugs. Ann. N.Y. Acad. Sci. 1187, 218-246.
156. Sotnikova, T.D., Beaulieu, J.M., Barak, L.S., Wetsel, W.C., Caron, M.G., and Gainetdinov, R.R. (2005). Dopamine-independent locomotor actions of amphetamines in a novel acute mouse mod-el of Parkinson disease. PLoS Biol. 3, e271.
157. Sprague, J.E. and Nichols, D.E. (1995). The monoamine oxidase-B inhibitor L-deprenyl protects against 3,4-methylenedioxyme-thamphetamine-induced lipid peroxidation and long-term sero-tonergic deficits. J. Pharmacol. Exp. Ther. 273, 667-673.
158. Stone, D.M., Stahl, D.C., Hanson, G.R., and 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.
159. Sulzer, D., Sonders, M.S., Poulsen, N.W., and Galli, A. (2005). Mechanism of neurotransmitter release by amphetamines, a review. Prog. Neurobiol. 75, 406-433.
160. Tancer, M. and Johanson, C.E. (2003). Reinforcing, subjective, and physiological effects of MDMA in humans, a comparison with D-amphetamine and mCPP. Drug Alcohol Depend. 72, 33-44.
161. Tassin, J.P. (2008). Uncoupling between noradrenergic and seroto-nergic neurons as a molecular basis of stable changes in behavior induced by repeated drugs of abuse. Biochem. Pharmacol. 75, 85-97.
162. Tourino, C., Ledent, C., Maldonado, R., and Valverde, O. (2008). CB1 cannabinoid receptor modulates 3,4-methylenedioxyme-thamphetamine acute responses and reinforcement. Biol. Psy-chiatry 63, 1030-1038.
163. Trigo, J.M., Renoir, T., Lanfumey, L., Hamon, M., Lesch, K.P., Robledo, P., and Maldonado, R. (2007). 3,4-Methylenedioxy-methamphetamine self-administration is abolished in serotonin transporter knockout mice. Biol. Psychiatry 62, 669-679.
164. Ujike, H. and Sato M. (2004). Clinical features of sensitization to methamphetamine observed in patients with methamphetamine dependence and psychosis. Ann. N.Y. Acad. Sci. 1025, 279-287.
165. Vaughan, R.A. (2004). Phosphorylation and regulation of psychos-timulant-sensitive neurotransmitter transporters. J. Pharmacol. Exp. Ther. 310, 1-7.
166. Volkow, N.D., Chang, L., Wang, GJ., Fowler, J.S., Leonido-Yee, M., Franceschi, D., Sedler, MJ., Gatley, SJ., Hitzemann, R., Ding, Y.S., et al. (2001). Association of dopamine transporter reduction with psychomotor impairment in methamphetamine abusers. Am. J. Psychiatry 158, 377-382.
167. Vollenweider, F.X., Liechti, M.E., and Paulus, M.P. (2005). MDMA affects both error-rate dependent and independent aspects of decision-making in a two-choice prediction task. J. Psychophar-macol. 19, 366-374.
168. White, F.J. and Kalivas, P.W. (1998). Neuroadaptations involved in amphetamine and cocaine addiction. Drug Alcohol Depend. 51, 141-153.
169. Wise, R.A. (2004). Dopamine, learning and motivation. Nat. Rev. Neurosci. 5, 483-494.
170. Xie, T., Tong, L., McLane, M.W., Hatzidimitriou, G., Yuan, J., McCann, U., and Ricaurte, G. (2006). Loss of serotonin trans-porter protein after MDMA and other ring-substituted amphet-amines. Neuropsychopharmacology 31, 2639-2651.
171. Yamamoto, B.K. and Raudensky, J. (2008). The role of oxidative stress, metabolic compromise, and inflammation in neuronal injury produced by amphetamine-related drugs of abuse. J. Neu-roimmune Pharmacol. 3, 203-217.
172. Yamamoto, B.K., Moszczynska, A., and Gudelsky, GA. (2010). Amphetamine toxicities: classical and emerging mechanisms. Ann. N.Y Acad. Sci. 1187, 101-121.
173. --dependent neurotransmitter transporters. Nature 437, 215-223.
174. Zakzanis, K.K., Campbell, Z., and Jovanovski, D. (2007). The neu-ropsychology of ecstasy (MDMA) use: a quantitative review. Hum. Psychopharmacol. 22, 427-435.
175. Zhao, Y., Terry, D., Shi, L., Weinstein, H., Blanchard, S.C., and Javitch, J.A. (2010). Single-molecule dynamics of gating in a neurotransmitter transporter homologue. Nature 465, 188-193.
176. Zolkowska, D., Rothman, R.B., and Baumann, M.H. (2006). Amphetamine analogs increase plasma serotonin: implications for cardiac and pulmonary disease. J. Pharmacol. Exp. Ther. 318, 604-610.