Neurotoxicity Research

, Volume 11, Issue 3–4, pp 183–202

Neurotoxicity of substituted amphetamines: Molecular and cellular mechanisms

  • Jean Lud Cadet
  • Irina N. Krasnova
  • Subramaniam Jayanthi
  • Johnalyn Lyles


The amphetamines, including amphetamine (AMPH), methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA), are among abused drugs in the US and throughout the world. Their abuse is associated with severe neurologic and psychiatric adverse events including the development of psychotic states. These neuropsychiatric complications might, in part, be related to drug-induced neurotoxic effects, which include damage to dopaminergic and serotonergic terminals, neuronal apoptosis, as well as activated astroglial and microglial cells in the brain. The purpose of the present review is to summarize the toxic effects of AMPH, METH and MDMA. The paper also presents some of the factors that are thought to underlie this toxicity. These include oxidative stress, hyperthermia, excitotoxicity and various apoptotic pathways. Better understanding of the cellular and molecular mechanisms involved in their toxicity should help to generate modern therapeutic approaches to prevent or attenuate the long-term consequences of amphetamine use disorders in humans.


Substituted amphetamines Methamphetamine Methylenedioxyamphetamine MDMA Serotoninergic neurons Dopaminergic neurons Hyperthermia Neurotoxicity 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abekawa T, T Ohmori and T Koyama (1994) Effects of repeated administration of a high dose of methamphetamine on dopamine and glutamate release in rat striatum and nucleus accumbens.Brain Res. 643, 276–281.PubMedGoogle Scholar
  2. Albers DS and PK Sonsalla (1995) Methamphetamine-induced hyperthermia and dopaminergic neurotoxicity in mice: pharmacological profile of protective and nonprotective agents.J. Pharmacol. Exp. Ther. 275, 1104–1114.PubMedGoogle Scholar
  3. Ali SF, JL Martin, MD Black and Y Itzhak (1999) Neuroprotective role of melatonin in methamphetamine-and 1 -methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurotoxicity. Ann.NYAcad. Sci. 890, 119.Google Scholar
  4. Alldredge BK, DH Lowenstein and RP Simon (1989) Seizures associated with recreational drug abuse.Neurology 39, 1037–1039.PubMedGoogle Scholar
  5. Amato JL, MG Bankson and BK Yamamoto (2006) Prior Exposure to chronic stress and MDMA potentiates meso-accumbens dopamine release mediated by the 5-HT(1B) receptor.Neuropsychopharmacology 2006 Aug 2; [Epub ahead of print].Google Scholar
  6. Asanuma M, T Hayashi, SV Ordonez, N Ogawa and JL Cadet (2000) Direct interactions of methamphetamine with the nucleus.Brain Res. Mol.Brain Res. 80, 237–243.PubMedGoogle Scholar
  7. Asanuma M, T Tsuji, I Miyazaki, K Miyoshi and N Ogawa (2003) Methamphetamine-induced neurotoxicity in mouse brain is attenuated by ketoprofen, a non-steroidal anti-inflammatory drug.Neurosci. Lett. 352, 13–16.PubMedGoogle Scholar
  8. Atlante A, P Calissano, A Bobba, S Giannattasio, E Marra and S Passarella (2001) Glutamate neurotoxicity, oxidative stress and mitochondria.FEBS Lett. 497, 1–5.PubMedGoogle Scholar
  9. Augsburger M, N Donze, A Menetrey, C Brossard, F Sporkert, C Giroud and P Mangin (2005) Concentration of drugs in blood of suspected impaired drivers.Forensic Sci. Int. 153, 11–15.PubMedGoogle Scholar
  10. Baker A and T Meert (2003) Morphine and d-amphetamine nullify each others’ hypothermic effects in mice.Pharmacol. Toxicol. 92, 64–70.PubMedGoogle Scholar
  11. Baldwin HA, MI Colado, TK Murray, RJ De Souza and AR Green (1993) Striatal dopamine releasein vivo following neurotoxic doses of methamphetamine and effect of the neuroprotective drugs, chlormethiazole and dizocilpine.Br. J. Pharmacol. 108, 590–596.PubMedGoogle Scholar
  12. Bankson MG and KA Cunningham (2001) 3,4-Methylenedio xymethamphetamine (MDMA) as a unique model of serotonin receptor function and serotonin-dopamine interactions.J. Pharmacol. Exp. Ther. 297, 846–852.PubMedGoogle Scholar
  13. Barnhart BC, EC Alappat and ME Peter (2003) The CD95 type I/type H model.Semin. Immunol. 15, 185–193.PubMedGoogle Scholar
  14. Bartu A, NC Freeman, GS Gawthorne, JP Codde and CD Holman (2004) Mortality in a cohort of opiate and amphetamine users in Perth, Western Australia.Addiction 99, 53–60.PubMedGoogle Scholar
  15. Battaglia G, SY Yeh, E O’Hearn, ME Molliver, MJ Kuhar and EB De Souza (1987) 3,4-Methylenedioxymethamphetamine 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
  16. Battaglia G, SY Yeh and EB De Souza (1988) MDMA-induced neurotoxicity: parameters of degeneration and recovery of brain serotonin neurons.Pharmacol. Biochem. Behav. 29, 269–274.PubMedGoogle Scholar
  17. Battaglia G, F Fornai, CL Busceti, G Aloisi, F Cerrito, A De Blasi, D Melchiorri and F Nicoletti (2002) Selective blockade of mGlu5 metabotropic glutamate receptors is protective against methamphetamine neurotoxicity.J. Neurosci. 22, 2135–2141.PubMedGoogle Scholar
  18. Berger UV, XF Gu, JW van Lange and EC Azmitia (1992) Evidence for a common mechanism of serotonin release induced by substituted amphetaminesin vitro.Ann. NY Acad. Sci. 648, 358–360.PubMedGoogle Scholar
  19. Betts ES, IN Krasnova, MT McCoy, B Ladenheim and JL Cadet (2002) Analysis of methamphetamine-induced changes in the expression of integrin family members in the cortex of wild-type and c-fos knockout mice.Neurotox. Res. 4, 617–623.PubMedGoogle Scholar
  20. Bolla KI, UD McCann and GA Ricaurte (1998) Memory impairment in abstinent MDMA (‘Ecstasy’) users.Neurology 51, 1532–1537.PubMedGoogle Scholar
  21. Bowyer JF, DL Davies, L Schmued, HW Broening, GD Newport, W Slikker Jr and RR Holson (1994) Further studies of the role of hyperthermia in methamphetamine neurotoxicity.J. Pharmacol. Exp. Ther. 268, 1571–1580.PubMedGoogle Scholar
  22. Brown TN, J Schulenberg, JG Bachman, PM O’Malley and LD Johnston (2001) Are risk and protective factors for substance use consistent across historical time?: national data from the high school classes of 1976 through 1997.Prev. Sci. 2, 29–43.PubMedGoogle Scholar
  23. Buchert R, J Obrocki, R Thomasius, O Vaterlein, K Petersen, L Jenicke, KH Bohuslavizki and M Clausen (2001) Long-term effects of ‘ecstasy’ abuse on the human brain studied by FDG PET.Nucl. Med. Commun. 22, 889–897.PubMedGoogle Scholar
  24. Buffenstein A, J Heaster and P Ko (1999) Chronic psychotic illness from methamphetamine.Am. J. Psychiatry 156, 662.PubMedGoogle Scholar
  25. Cadet JL and C Brannock (1998) Free radicals and the pathobiology of brain dopamine systems.Neurochem. Int. 32, 117–131.PubMedGoogle Scholar
  26. Cadet JL, S Ali and C Epstein (1994a) Involvement of oxygen-based radicals in methamphetamine-induced neurotoxicity: evidence from the use of CuZnSOD transgenic mice.Ann. NY Acad. Sci. 738, 388–391.Google Scholar
  27. Cadet JL, B Ladenheim, I Baum, E Carlson and C Epstein (1994b) CuZn-superoxide dismutase (CuZnSOD) transgenic mice show resistance to the lethal effects of methylene-dioxyamphetamine (MDA) and of methylenedioxymetham-phetamine (MDMA).Brain Res. 655, 259–262.Google Scholar
  28. Cadet JL, B Ladenheim, H Hirata, RB Rothman, S Ali, E Carlson, C Epstein and TH Moran (1995) Superoxide radicals mediate the biochemical effects of methylene-dioxymethamphetamine (MDMA): evidence from using CuZn-superoxide dismutase transgenic mice.Synapse 21, 169–176.PubMedGoogle Scholar
  29. Cadet JL,SV Ordonezand and JV Ordonez(1997)Methamphetamine induces apoptosis in immortalized neural cells: protection by the proto-oncogene, bcl-2.Synapse 25, 176–184.PubMedGoogle Scholar
  30. Cadet JL, S Jayanthi, MT McCoy, M Vawter and B Ladenheim (2001) Temporal profiling of methamphetamine-induced changes in gene expression in the mouse brain: evidence from cDNA array.Synapse 41, 40–48.PubMedGoogle Scholar
  31. Cadet JL, MT McCoy and B Ladenheim (2002) Distinct gene expression signatures in the striata of wild-type and heterozygous c-fos knockout mice following methamphetamine administration: evidence from cDNA array analyses.Synapse 44, 211–226.PubMedGoogle Scholar
  32. Cadet JL, S Jayanthi and X Deng (2003) Speed kills: cellular and molecular bases of methamphetamine-induced nerve terminal degeneration and neuronal apoptosis.FASEB J. 17, 1775–1788.PubMedGoogle Scholar
  33. Cadet JL, S Jayanthi and X Deng (2005) Methamphetamine-induced neuronal apoptosis involves the activation of multiple death pathways. Review.Neurotox. Res. 8, 199–208.PubMedGoogle Scholar
  34. Callahan BT, BJ Cord, J Yuan, UD McCann and GA Ricaurte (2001) Inhibitors of Na(+)/H(+) and Na(+)/Ca(2+) exchange potentiate methamphetamine-induced dopamine neurotoxicity: possible role of ionic dysregulation in methamphetamine neurotoxicity.J. Neurochem. 77, 1348–1362.PubMedGoogle Scholar
  35. Callaway CW and RF Clark (1994) Hyperthermia in psycho- stimulant overdose.Ann. Emerg. Med. 24, 68–76.PubMedGoogle Scholar
  36. Cho AK and WP Melega (2002) Patterns of methamphetamine abuse and their consequences.J. Addict. Dis. 21, 21–34.PubMedGoogle Scholar
  37. Choi C and EN Benveniste (2004) Fas ligand/Fas system in the brain: regulator of immune and apoptotic responses.Brain Res. Brain Res. Rev. 44, 65–81.PubMedGoogle Scholar
  38. Chowdhury I, B Tharakan and GK Bhat (2006) Current concepts in apoptosis: the physiological suicide program revisited.Cell. Mol. Biol. Lett. 11, 506–525.PubMedGoogle Scholar
  39. Chung KK, TM Dawson and VL Dawson (2005) Nitric oxide, S-nitrosylation and neurodegeneration.Cell Mol. Biol. (Noisy-le-grand) 51, 247–254.Google Scholar
  40. Chynn KY (1968) Technique for experimental embolization of cerebral arteries and repetitive selective internal carotid arteriography in dogs.Invest. Radiol. 3, 275–279.PubMedGoogle Scholar
  41. Clausing P and JF Bowyer (1999) Time course of brain temperature and caudate/putamen microdialysate levels of amphetamine and dopamine in rats after multiple doses of d-amphetamine.Ann. NY Acad. Sci. 890, 495–504.PubMedGoogle Scholar
  42. Clausing P, B Gough, RR Holson, W Slikker Jr and JF Bowyer (1995) Amphetamine levels in brain microdialysate, caudate/putamen, substantia nigra and plasma after dosage that produces either behavioral or neurotoxic effects.J. Pharmacol. Exp. Ther. 274, 614–621.PubMedGoogle Scholar
  43. Colado MI and AR Green (1994) A study of the mechanism of MDMA (‘ecstasy’)-induced neurotoxicity of 5-HT neurones using chlormethiazole, dizocilpine and other protective compounds.Br. J. Pharmacol. 111, 131–136.PubMedGoogle Scholar
  44. Colado MI and AR Green (1995) The spin trap reagent alpha- phenyl-N-tert-butyl nitrone prevents ‘ecstasy’-induced neurodegeneration of 5-hydroxytryptamine neurones.Eur. J. Pharmacol. 280, 343–346.PubMedGoogle Scholar
  45. Colado MI, TK Murray and AR Green (1993) 5-HT loss in rat brain following 3,4-methylenedioxymethamphetamine (MDMA), p-chloroamphetamine and fenfluramine administration and effects of chlormethiazole and dizocilpine.Br. J. Pharmacol. 108, 583–589.PubMedGoogle Scholar
  46. Commins DL, G Vosmer, RM Virus, WL Woolverton, CR Schuster and LS Seiden (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
  47. Craig AL and HJ Kupferberg (1972) Hyperthermia in damphetamine toxicity in aggregated mice of different strains.J. Pharmacol. Exp. Ther. 180, 616–624.PubMedGoogle Scholar
  48. Cubells JF, S Rayport, G Rajendran and D Sulzer (1994) Methamphetamine neurotoxicity involves vacuolation of endocytic organelles and dopamine-dependent intracellular oxidative stress.J. Neurosci. 14, 2260–2271.PubMedGoogle Scholar
  49. Culmsee C and MP Mattson (2005) p53 in neuronal apoptosis.Biochem. Biophys. Res. Commun. 331, 761–777.PubMedGoogle Scholar
  50. Dafters RI (1995) Hyperthermia following MDMA administration in rats: effects of ambient temperature, water consumption, and chronic dosing.Physiol. Behav. 58, 877–882.PubMedGoogle Scholar
  51. Dafters RI and E Lynch (1998) Persistent loss of thermoregulation in the rat induced by 3,4-methylenedioxymethamphet-amine (MDMA or “Ecstasy”) but not by fenfluramine.Psychopharmacology (Berl.) 138, 207–212.Google Scholar
  52. Dalton TP, HG Shertzer and A Puga (1999) Regulation of gene expression by reactive oxygen.Annu. Rev. Pharmacol. Toxicol. 39, 67–101.PubMedGoogle Scholar
  53. Dawson VL and TM Dawson (1998) Nitric oxide in neurode-generation.Prog. Brain Res. 118, 215–229.PubMedGoogle Scholar
  54. De Letter EA, MH Piette, WE Lambert and JA Cordonnier (2006) Amphetamines as potential inducers of fatalities: a review in the district of Ghent from 1976-2004.Med. Sci. Law 46, 37–65.PubMedGoogle Scholar
  55. De Souza EB, G Battaglia and TR Insel (1990) Neurotoxic effect of MDMA on brain serotonin neurons: evidence from neurochemical and radioligand binding studies.Ann. NY Acad. Sci. 600, 682–697; discussion 697-688.PubMedGoogle Scholar
  56. De Vito MJ and GC Wagner (1989) Methamphetamine- induced neuronal damage: a possible role for free radicals.Neuropharmacology 28, 1145–1150.PubMedGoogle Scholar
  57. Deng X and JL Cadet (2000) Methamphetamine-induced apoptosis is attenuated in the striata of copper-zinc superoxide dismutase transgenic mice.Brain Res. Mol. Brain Res. 83, 121–124.PubMedGoogle Scholar
  58. Deng X, B Ladenheim, LI Tsao and JL Cadet (1999) Null mutation of c-fos causes exacerbation of methamphetamine-induced neurotoxicity.J. Neurosci. 19, 10107–10115.PubMedGoogle Scholar
  59. Deng X, Y Wang, J Chou and JL Cadet (2001) Methamphetamine causes widespread apoptosis in the mouse brain: evidence from using an improved TUNEL histochemical method.Brain Res. Mol. Brain Res. 93, 64–69.PubMedGoogle Scholar
  60. Deng X, NS Cai, MT McCoy, W Chen, MA Trush and JL Cadet (2002a) Methamphetamine induces apoptosis in an immortalized rat striatal cell line by activating the mitochondrial cell death pathway.Neuropharmacology 42, 837–845.Google Scholar
  61. Deng X, S Jayanthi, B Ladenheim, IN Krasnova and JL Cadet (2002b) Mice with partial deficiency of c-Jun show attenuation of methamphetamine-induced neuronal apoptosis.Mol. Pharmacol. 62, 993–1000.Google Scholar
  62. Derlet RW, P Rice, BZ Horowitz and RV Lord (1989) Amphetamine toxicity: experience with 127 cases.J. Emerg. Med. 7, 157–161.PubMedGoogle Scholar
  63. Dore G and M Sweeting (2006) Drug-induced psychosis associated with crystalline methamphetamine.Australas Psychiatry 14, 86–89.PubMedGoogle Scholar
  64. Droin NM, MJ Pinkoski, E Dejardin and DR Green (2003) Egr family members regulate nonlymphoid expression of Fas ligand, TRAIL, and tumor necrosis factor during immune responses.Mol. Cell. Biol. 23, 7638–7647.PubMedGoogle Scholar
  65. Eisch AJ and JF Marshall (1998) Methamphetamine neurotoxicity: dissociation of striatal dopamine terminal damage from parietal cortical cell body injury.Synapse 30, 433–445.PubMedGoogle Scholar
  66. Ellison G, MS Eison, HS Huberman and F Daniel (1978) Long-term changes in dopaminergic innervation of caudate nucleus after continuous amphetamine administration.Science 201, 276–278.PubMedGoogle Scholar
  67. Farfel GM and LS Seiden (1995) Role of hypothermia in the mechanism of protection against serotonergic toxicity. II. Experiments with methamphetamine, p-chloroamphet-amine, fenfluramine, dizocilpine and dextromethorphan.J. Pharmacol. Exp. Ther. 272, 868–875.PubMedGoogle Scholar
  68. Farfel GM, GL Vosmer and LS Seiden (1992) The N-methyl- D-aspartate antagonist MK-801 protects against serotonin depletions induced by methamphetamine, 3,4-methylene- dioxymethamphetamine and p-chloroamphetamine.Brain Res. 595, 121–127.PubMedGoogle Scholar
  69. Farrell M, J Marsden, R Ali and W Ling (2002) Methamphetamine: drug use and psychoses becomes a major public health issue in the Asia Pacific region.Addiction 97, 771–772.PubMedGoogle Scholar
  70. Ferguson SM, CS Norton, SJ Watson, H Akil and TE Robinson (2003) Amphetamine-evoked c-fos mRNA expression in the caudate-putamen: the effects of DA and NMDA receptor antagonists vary as a function of neuronal phenotype and environmental context.J. Neurochem. 86, 33–44.PubMedGoogle Scholar
  71. Ferri KF and G Kroemer (2001) Organelle-specific initiation of cell death pathways.Nat. Cell. Biol. 3, E255-E263.PubMedGoogle Scholar
  72. Fischer C, G Hatzidimitriou, J Wlos, J Katz and G Ricaurte (1995) Reorganization of ascending 5-HT axon projec- tions in animals previously exposed to the recreational drug (+/-)3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”).J. Neurosci. 15, 5476–5485.PubMedGoogle Scholar
  73. Fukami G, K Hashimoto, K Koike, N Okamura, E Shimizu and M Iyo (2004) Effect of antioxidant N-acetyl-L-cysteine on behavioral changes and neurotoxicity in rats after administration of methamphetamine.Brain Res. 1016, 90–95.PubMedGoogle Scholar
  74. Fumagalli F, RR Gainetdinov, KJ Valenzano and MG Caron (1998) Role of dopamine transporter in methamphetamine- induced neurotoxicity: evidence from mice lacking the transporter.J. Neurosci. 18, 4861–4869.PubMedGoogle Scholar
  75. Gerra G, A Zaimovic, M Ferri, U Zambelli, M Timpano, E Neri, GF Marzocchi, R Delsignore and F Brambilla (2000) Long- lasting effects of (+/-)3,4-methylenedioxymethamphetamine (ecstasy) on serotonin system function in humans.Biol. Psychiatry 47, 127–136.PubMedGoogle Scholar
  76. Gilcrease MZ (2007) Integrin signaling in epithelial cells.Cancer Lett. 247, 1–25.PubMedGoogle Scholar
  77. Ginsberg MD, M Hertzman and WW Schmidt-Nowara (1970) Amphetamine intoxication with coagulopathy, hyperther-mia, and reversible renal failure. A syndrome resembling heatstroke.Ann. Intern. Med. 73, 81–85.PubMedGoogle Scholar
  78. Gluck MR, LY Moy, E Jayatilleke, KA Hogan, L Manzino and PK Sonsalla (2001) Parallel increases in lipid and protein oxidative markers in several mouse brain regions after meth- amphetamine treatment.J. Neurochem. 79, 152–160.PubMedGoogle Scholar
  79. Gordon CJ, WP Watkinson, JP O’Callaghan and DB Miller (1991) Effects of 3,4-methylenedioxymethamphetamine on autonomic thermoregulatory responses of the rat.Pharmacol. Biochem. Behav. 38, 339–344.PubMedGoogle Scholar
  80. Gudelsky GA and JF Nash (1996) Carrier-mediated release of serotonin by 3,4-methylenedioxymethamphetamine: implications for serotonin-dopamine interactions.J. Neurochem. 66, 243–249.PubMedGoogle Scholar
  81. Gustavsen I, J Morland and JG Bramness (2006) Impairment related to blood amphetamine and/or methamphetamine concentrations in suspected drugged drivers.Accid. Anal. Prev. 38, 490–495.PubMedGoogle Scholar
  82. Harold C, T Wallace, R Friedman, G Gudelsky and B Yamamoto (2000) Methamphetamine selectively alters brain glutathione.Eur. J. Pharmacol. 400, 99–102.PubMedGoogle Scholar
  83. Hatzidimitriou G, UD McCann and GA Ricaurte (1999) Altered serotonin innervation patterns in the forebrain of monkeys treated with (+/-)3,4-methylenedioxymethamphet-amine seven years previously: factors influencing abnormal recovery.J. Neurosci. 19, 5096–5107.PubMedGoogle Scholar
  84. Hirata H, B Ladenheim, E Carlson, C Epstein and JL Cadet (1996) Autoradiographic evidence for methamphetamine- induced striatal dopaminergic loss in mouse brain: attenuation in CuZn-superoxide dismutase transgenic mice.Brain Res. 714, 95–103.PubMedGoogle Scholar
  85. Hsieh P (2001) Molecular mechanisms of DNA mismatch repair.Mutat. Res. 486, 71–87.PubMedGoogle Scholar
  86. Huang NK, FJ Wan, CJ Tseng and CS Tung(1997) Amphetamine induces hydroxyl radical formation in the striatum of rats.Life Sci. 61, 2219–2229.PubMedGoogle Scholar
  87. Hughes PE, T Alexi, CE Williams, RG Clark and PD Gluckman (1999) Administration of recombinant human Activin-A has powerful neurotrophic effects on select striatal phenotypes in the quinolinic acid lesion model of Huntington’s disease.Neuroscience 92, 197–209.PubMedGoogle Scholar
  88. Imai Y and S Kohsaka (2002) Intracellular signaling in M-CSF-induced microglia activation: role of Iba1.Glia 40, 164–174.PubMedGoogle Scholar
  89. Imam SZ and SF Ali (2000) Selenium, an antioxidant, attenuates methamphetamine-induced dopaminergic toxicity and peroxynitrite generation.Brain Res. 855, 186–191.PubMedGoogle Scholar
  90. Imam SZ, GD Newport, Y Itzhak, JL Cadet, F Islam, W Slikker Jr and SF Ali (2001) Peroxynitrite plays a role in methamphetamine-induced dopaminergic neurotoxicity: evidence from mice lacking neuronal nitric oxide synthase gene or overexpressing copper-zinc superoxide dismutase.J. Neurochem. 76, 745–749.PubMedGoogle Scholar
  91. Insel TR, G Battaglia, JN Johannessen, S Marra and EB De Souza (1989) 3,4-Methylenedioxymethamphetamine (“ecstasy”) selectively destroys brain serotonin terminals in rhesus monkeys.J. Pharmacol. Exp. Ther. 249, 713–720.PubMedGoogle Scholar
  92. Itzhak Y and SF Ali (2006) Role of nitrergic system in behavioral and neurotoxic effects of amphetamine analogs.Pharmacol. Ther. 109, 246–262.PubMedGoogle Scholar
  93. Itzhak Y, C Gandia, PL Huang and SF Ali (1998) Resistance of neuronal nitric oxide synthase-deficient mice to methamphetamine-induced dopaminergic neurotoxicity.J. Pharmacol. Exp. Ther. 284, 1040–1047.PubMedGoogle Scholar
  94. Itzhak Y, JL Martin and SF Ali (2000) nNOS inhibitors attenuate methamphetamine-induced dopaminergic neurotoxicity but not hyperthermia in mice.Neuroreport 11, 2943–2946.PubMedGoogle Scholar
  95. Iversen L (2006) Neurotransmitter transporters and their impact on the development of psychopharmacology.Br. J. Pharmacol. 147 Suppl. 1, S82-S88.Google Scholar
  96. Jakab RL and JF Bowyer (2002) Parvalbumin neuron circuits and microglia in three dopamine-poor cortical regions remain sensitive to amphetamine exposure in the absence of hyperthermia, seizure and stroke.Brain Res. 958, 52–69.PubMedGoogle Scholar
  97. Janowsky DS and C Risch (1979) Amphetamine psychosis and psychotic symptoms.Psychopharmacology (Berl.) 65, 73–77.Google Scholar
  98. Jayanthi S, B Ladenheimand JL Cadet (1998) Methamphetamine- induced changes in antioxidant enzymes and lipid peroxidation in copper/zinc-superoxide dismutase transgenic mice.Ann. NYAcad. Sci. 844, 92–102.Google Scholar
  99. Jayanthi S, B Ladenheim, AM Andrews and JL Cadet (1999) Overexpression of human copper/zinc superoxide dismutase in transgenic mice attenuates oxidative stress caused by methylenedioxymethamphetamine (ecstasy).Neuroscience 91, 1379–1387.PubMedGoogle Scholar
  100. Jayanthi S, X Deng, M Bordelon, MT McCoy and JL Cadet (2001) Methamphetamine causes differential regulation of pro-death and anti-death Bcl-2 genes in the mouse neocortex.FASEBJ. 15, 1745–1752.Google Scholar
  101. Jayanthi S, X Deng, PA Noailles, B Ladenheim and JL Cadet (2004) Methamphetamine induces neuronal apoptosis via cross-talks between endoplasmic reticulum and mitochon- dria-dependent death cascades.FASEBJ. 18, 238–251.Google Scholar
  102. Jayanthi S, X Deng, B Ladenheim, MT McCoy, A Cluster, NS Cai and JL Cadet (2005) Calcineurin/NFAT-induced up- regulation of the Fas ligand/Fas death pathway is involved in methamphetamine-induced neuronal apoptosis.Proc. Natl. Acad. Sci. USA 102, 868–873.PubMedGoogle Scholar
  103. Johnson M, GR Hanson and JW Gibb (1989) Effect of MK- 801 on the decrease in tryptophan hydroxylase induced by methamphetamine and its methylenedioxy analog.Eur. J. Pharmacol. 165, 315–318.PubMedGoogle Scholar
  104. Jones AW (2005) Driving under the influence of drugs in Sweden with zero concentration limits in blood for controlled substances.Traffic Inj. Prev. 6, 317–322.PubMedGoogle Scholar
  105. Jori A and M Rutczynski (1978) A genetic analysis of the hyperthermic response to d-amphetamine in two inbred strains of mice.Psychopharmacology (Berl.) 59, 199–203.Google Scholar
  106. Kalant H and OJ Kalant (1975) Death in amphetamine users: causes and rates.Can. Med. Assoc. J. 112, 299–304.PubMedGoogle Scholar
  107. Kil HY, J Zhang and CA Piantadosi (1996) Brain temperature alters hydroxyl radical production during cerebral isch- emia/reperfusion in rats.J. Cereb. Blood Flow Metab. 16, 100–106.PubMedGoogle Scholar
  108. Kish SJ, Y Furukawa, L Ang, SP Vorce and KS Kalasinsky (2000) Striatal serotonin is depleted in brain of a human MDMA (ecstasy) user.Neurology 55, 294–296.PubMedGoogle Scholar
  109. Kondo T, T Ito and Y Sugita (1994) Bromocriptine scavenges methamphetamine-induced hydroxyl radicals and attenuates dopamine depletion in mouse striatum.Ann. NY Acad. Sci. 738, 222–229.PubMedGoogle Scholar
  110. Kostowski W, A Plaznik, O Pucilowski and E Malatynska (1982) Effect of lesions of the brain noradrenergic systems on amphetamine-induced hyperthermia and locomotor stimulation.Acta Physiol. Pol. 33, 383–387.PubMedGoogle Scholar
  111. Krasnova IN, B Ladenheim, S Jayanthi, J Oyler, TH Moran, MA Huestis and JL Cadet (2001) Amphetamine-induced toxicity in dopamine terminals in CD-1 and C57BL/6J mice: complex roles for oxygen-based species and temperature regulation.Neuroscience 107, 265–274.PubMedGoogle Scholar
  112. Krasnova IN, MT McCoy, B Ladenheim and JL Cadet (2002) cDNA array analysis of gene expression profiles in the stri- ata of wild-type and Cu/Zn superoxide dismutase transgenic mice treated with neurotoxic doses of amphetamine.FASEB J. 16, 1379–1388.PubMedGoogle Scholar
  113. Krasnova IN, B Ladenheim and JL Cadet (2005) Amphetamine induces apoptosis of medium spiny striatal projection neurons via the mitochondria-dependent pathway.FASEB J. 19, 851–853.PubMedGoogle Scholar
  114. Krieglstein K, C Suter-Crazzolara, WH Fischer and K Unsicker (1995) TGF-beta superfamily members promote survival of midbrain dopaminergic neurons and protect them against MPP+ toxicity.EMBOJ. 14, 736–742.Google Scholar
  115. Ladeby R, M Wirenfeldt, D Garcia-Ovejero, C Fenger, L Dissing-Olesen, I Dalmau and B Finsen (2005) Microglial cell population dynamics in the injured adult central nervous system.Brain Res. Brain Res. Rev. 48, 196–206.PubMedGoogle Scholar
  116. Lan KC, YF Lin, FC Yu, CS Lin and P Chu (1998) Clinical manifestations and prognostic features of acute methamphet-amine intoxication.J. Formos. Med. Assoc. 97, 528–533.PubMedGoogle Scholar
  117. LaVoie MJ and TG Hastings (1999) Dopamine quinone formation and protein modification associated with the striatal neurotoxicity of methamphetamine: evidence against a role for extracellular dopamine.J. Neurosci. 19, 1484–1491.PubMedGoogle Scholar
  118. LaVoie MJ, JP Card and TG Hastings (2004) Microglial activation precedes dopamine terminal pathology in methamphetamine-induced neurotoxicity.Exp. Neurol. 187, 47–57.PubMedGoogle Scholar
  119. Levine AS, DC Jewett, JP Cleary, CM Kotz and CJ Billington (2004) Our journey with neuropeptide Y: effects on ingestive behaviors and energy expenditure.Peptides 25, 505–510.PubMedGoogle Scholar
  120. Lew R, KE Sabol, C Chou, GL Vosmer, J Richards and LS Seiden (1996) Methylenedioxymethamphetamine-induced serotonin deficits are followed by partial recovery over a 52-week period. Part II: Radioligand binding and autoradi-ography studies.J. Pharmacol. Exp. Ther. 276, 855–865.PubMedGoogle Scholar
  121. Li Y and MA Trush (1993) DNA damage resulting from the oxidation of hydroquinone by copper: role for a Cu(II)/Cu(I) redox cycle and reactive oxygen generation.Carcinogenesis 14, 1303–1311.PubMedGoogle Scholar
  122. Li-Weber M and PH Krammer (2002) The death of a T-cell: expression of the CD95 ligand.Cell Death Differ. 9, 101–103.PubMedGoogle Scholar
  123. Li-Weber M, O Laur and PH Krammer (1999) Novel Egr/NF- AT composite sites mediate activation of the CD95 (APO-1/Fas) ligand promoter in response to T cell stimulation.Eur. J. Immunol. 29, 3017–3027.PubMedGoogle Scholar
  124. Liechti ME, C Baumann, A Gamma and FX Vollenweider (2000) Acute psychological effects of 3,4-methyl- enedioxymethamphetamine (MDMA, “ecstasy”) are attenuated by the serotonin uptake inhibitor citalopram.Neuropsychopharmacology 22, 513–521.PubMedGoogle Scholar
  125. Lin PS, S Quamo, KC Ho and J Gladding (1991) Hyperthermia enhances the cytotoxic effects of reactive oxygen species to Chinese hamster cells and bovine endothelial cellsin vitro.Radiat. Res. 126, 43–51.PubMedGoogle Scholar
  126. Locksley RM, N Killeen and MJ Lenardo (2001) The TNF and TNF receptor superfamilies: integrating mammalian biology.Cell 104, 487–501.PubMedGoogle Scholar
  127. Lombard DB, KF Chua, R Mostoslavsky, S Franco, M Gostissa and FW Alt (2005) DNA repair, genome stability, and aging.Cell 120, 497–512.PubMedGoogle Scholar
  128. London ED, SL Simon, SM Berman, MA Mandelkern, AM Lichtman, J Bramen, AK Shinn, K Miotto, J Learn, Y Dong, JA Matochik, V Kurian, T Newton, R Woods, R Rawson and W Ling (2004) Mood disturbances and regional cerebral metabolic abnormalities in recently abstinent methamphetamine abusers.Arch. Gen. Psychiatry 61, 73–84.PubMedGoogle Scholar
  129. Lotharius J and KL O’Malley (2001) Role of mitochondrial dysfunction and dopamine-dependent oxidative stress in amphetamine-induced toxicity.Ann. Neurol. 49, 79–89.PubMedGoogle Scholar
  130. Lyles J and JL Cadet (2003) Methylenedioxymeth-amphetamine (MDMA, Ecstasy) neurotoxicity: cellular and molecular mechanisms.Brain Res. Brain Res. Rev. 42, 155–168.PubMedGoogle Scholar
  131. Macario AJ and E Conway de Macario (2005) Sick chaperones, cellular stress, and disease.N. Engl. J. Med. 353, 1489–1501.PubMedGoogle Scholar
  132. Malberg JE, KE Sabol and LS Seiden (1996) Co-administration of MDMA with drugs that protect against MDMA neurotoxicity produces different effects on body temperature in the rat.J. Pharmacol. Exp. Ther. 278, 258–267.PubMedGoogle Scholar
  133. Mark KA, JJ Soghomonian and BK Yamamoto (2004) High-dose methamphetamine acutely activates the striatonigral pathway to increase striatal glutamate and mediate long-term dopamine toxicity.J. Neurosci. 24, 11449–11456.PubMedGoogle Scholar
  134. Marshall JF, SJ O’Dell and FB Weihmuller (1993) Dopamine-glutamate interactions in methamphetamine-induced neurotoxicity.J. Neural Transm. Gen. Sect. 91, 241–254.PubMedGoogle Scholar
  135. Martin SS and K Vuori (2004) Regulation of Bcl-2 proteins during anoikis and amorphosis.Biochim. Biophys. Acta 1692, 145–157.PubMedGoogle Scholar
  136. Matthews RT, TH Champney and GD Frye (1989) Effects of (+-)3,4-methylenedioxymethamphetamine (MDMA) on brain dopaminergic activity in rats.Pharmacol. Biochem. Behav. 33, 741–747.PubMedGoogle Scholar
  137. McCabe SE, CJ Teter and CJ Boyd (2004) The use, misuse and diversion of prescription stimulants among middle and high school students.Subst. Use Misuse 39, 1095–1116.PubMedGoogle Scholar
  138. McCabe SE, JR Knight, CJ Teter and H Wechsler (2005) Non- medical use of prescription stimulants among US college students: prevalence and correlates from a national survey.Addiction 100, 96–106.PubMedGoogle Scholar
  139. McCann UD, A Ridenour, Y Shaham and GA Ricaurte (1994) Serotonin neurotoxicity after (+/-)3,4-methylenedioxymeth- amphetamine (MDMA; “ecstasy”): a controlled study in humans.Neuropsychopharmacology 10, 129–138.PubMedGoogle Scholar
  140. McCann UD, Z Szabo, U Scheffel, RF Dannals and GA Ricaurte (1998a) Positron emission tomographic evidence of toxic effect of MDMA (“ecstasy”) on brain serotonin neurons in human beings.Lancet 352, 1433–1437.Google Scholar
  141. McCann UD, DF Wong, F Yokoi, V Villemagne, RF Dannals and GA Ricaurte (1998b) Reduced striatal dopamine transporter density in abstinent methamphetamine and methcathi-none users: evidence from positron emission tomography studies with [11C]WIN-35,428.J. Neurosci. 18, 8417–8422.Google Scholar
  142. McCann UD, M Mertl, V Eligulashvili and GA Ricaurte (1999) Cognitive performance in (+/-) 3,4-methylenedioxymeth-amphetamine (MDMA, “ecstasy”) users: a controlled study.Psychopharmacology (Berl.) 143, 417–425.Google Scholar
  143. McCann UD, V Eligulashvili and GA Ricaurte (2000) (+/-)3,4- Methylenedioxymethamphetamine (“ecstasy”)-induced serotonin neurotoxicity: clinical studies.Neuropsychobiology 42, 11–16.PubMedGoogle Scholar
  144. McCullough KD, JL Martindale, LO Klotz, TY Aw and NJ Holbrook (2001) Gadd153 sensitizes cells to endoplasmic reticulum stress by down-regulating Bcl2 and perturbing the cellular redox state.Mol. Cell. Biol. 21, 1249–1259.PubMedGoogle Scholar
  145. McKenna DJ and SJ Peroutka (1990) Neurochemistry and neurotoxicity of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”).J. Neurochem. 54, 14–22.PubMedGoogle Scholar
  146. McKetin R and RP Mattick (1997) Attention and memory in illicit amphetamine users.Drug Alcohol Depend. 48, 235–242.PubMedGoogle Scholar
  147. Mechan AO, B Esteban, E O’Shea, JM Elliott, MI Colado and AR Green (2002) The pharmacology of the acute hyperthermic response that follows administration of 3,4-methylene-dioxymethamphetamine (MDMA, ‘ecstasy’) to rats.Br. J. Pharmacol. 135, 170–180.PubMedGoogle Scholar
  148. Milanovic D, V Pesic, L Rakic, S Kanazir and S Ruzdijic (2006) Enhancement of AP-1 DNA-binding activity during amphetamine- and phencyclidine-mediated behaviour in rats.Neuropharmacology 50, 924–933.PubMedGoogle Scholar
  149. Miller DB and JP O’Callaghan (1994) Environment-, drug- and stress-induced alterations in body temperature affect the neurotoxicity of substituted amphetamines in the C57BL/6J mouse.J. Pharmacol. Exp. Ther. 270, 752–760.PubMedGoogle Scholar
  150. Miller DB and JP O’Callaghan (1996) Neurotoxicity of damphetamine in the C57BL/6J and CD-1 mouse. Interactions with stress and the adrenal system.Ann. NYAcad. Sci. 801, 148–167.Google Scholar
  151. Mills EM, ML Banks, JE Sprague and T Finkel (2003) Pharmacology: uncoupling the agony from ecstasy.Nature 426, 403–404.PubMedGoogle Scholar
  152. Miyazaki I, M Asanuma, FJ Diaz-Corrales, M Fukuda, K Kitaichi, K Miyoshi and N Ogawa (2006) Methamphet-amine-induced dopaminergic neurotoxicity is regulated by quinone-formation-related molecules.FASEB J. 20, 571–573.PubMedGoogle Scholar
  153. Moll UM, S Wolff, D Speidel and W Deppert (2005) Transcription-independent pro-apoptotic functions of p53.Curr. Opin. Cell. Biol. 17, 631–636.PubMedGoogle Scholar
  154. Molliver ME, UV Berger, LA Mamounas, DC Molliver, E O’Hearn and MA Wilson (1990) Neurotoxicity of MDMA and related compounds: anatomic studies.Ann. NY Acad. Sci. 600, 649–661; discussion 661-644.PubMedGoogle Scholar
  155. Murachi T, K Tanaka, M Hatanaka and T Murakami (1980) Intracellular Ca2+-dependent protease (calpain) and its high- molecular-weight endogenous inhibitor (calpastatin).Adv. Enzyme Regul. 19, 407–424.PubMedGoogle Scholar
  156. Murray JB (1998) Psychophysiological aspects of amphet-amine-methamphetamine abuse.J. Psychol. 132, 227–237.PubMedGoogle Scholar
  157. Nagata S (1999) Fas ligand-induced apoptosis.Annu. Rev. Genet. 33, 29–55.PubMedGoogle Scholar
  158. Nakagawa T and J Yuan (2000) Cross-talk between two cyste- ine protease families. Activation of caspase-12 by calpain in apoptosis.J. Cell. Biol. 150, 887–894.PubMedGoogle Scholar
  159. Nash JFJr, HY Meltzer and GA Gudelsky (1988) Elevation of serum prolactin and corticosterone concentrations in the rat after the administration of 3,4-methylenedioxymethamphet- amine.J. Pharmacol. Exp. Ther. 245, 873–879.PubMedGoogle Scholar
  160. Nilsen H and HE Krokan (2001) Base excision repair in a network of defense and tolerance.Carcinogenesis 22, 987–998.PubMedGoogle Scholar
  161. O’Dell SJ and JF Marshall (2000) Repeated administration of methamphetamine damages cells in the somatosensory cortex: overlap with cytochrome oxidase-rich barrels.Synapse 37, 32–37.PubMedGoogle Scholar
  162. O’Hearn E, G Battaglia, EB De Souza, MJ Kuhar and ME Molliver (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
  163. O’Shea E, I Escobedo, L Orio, V Sanchez, M Navarro, AR Green and MI Colado (2005) Elevation of ambient room temperature has differential effects on MDMA-induced 5-HT and dopamine release in striatum and nucleus accum- bens of rats.Neuropsychopharmacology 30, 1312–1323.PubMedGoogle Scholar
  164. Oliveira MT, AC Rego, MT Morgadinho, TR Macedo and CR Oliveira (2002) Toxic effects of opioid and stimulant drugs on undifferentiated PC12 cells.Ann. NY Acad. Sci. 965, 487–496.PubMedGoogle Scholar
  165. Ornstein TJ, JL Iddon, AM Baldacchino, BJ Sahakian, M London, BJ Everitt and TW Robbins (2000) Profiles of cognitive dysfunction in chronic amphetamine and heroin abusers.Neuropsychopharmacology 23, 113–126.PubMedGoogle Scholar
  166. Papp E, G Nardai, C Soti and P Csermely (2003) Molecular chaperones, stress proteins and redox homeostasis.Biofactors 17, 249–257.PubMedGoogle Scholar
  167. Paris JM and KA Cunningham (1992) Lack of serotonin neurotoxicity after intraraphe microinjection of (+)-3,4-methy-lenedioxymethamphetamine (MDMA).Brain Res. Bull. 28, 115–119.PubMedGoogle Scholar
  168. Paschen W (2001) Dependence of vital cell function on endoplasmic reticulum calcium levels: implications for the mechanisms underlying neuronal cell injury in different pathological states.Cell Calcium 29, 1–11.PubMedGoogle Scholar
  169. Persico AM, CW Schindler, R Zaczek, MT Brannock and GR Uhl (1995) Brain transcription factor gene expression, neurotransmitter levels, and novelty response behaviors: alterations during rat amphetamine withdrawal and following chronic injection stress.Synapse 19, 212–227.PubMedGoogle Scholar
  170. Petit C and A Sancar (1999) Nucleotide excision repair: from E. coli to man.Biochimie 81, 15–25.PubMedGoogle Scholar
  171. Poli G, G Leonarduzzi, F Biasi and E Chiarpotto (2004) Oxidative stress and cell signalling.Curr. Med. Chem. 11, 1163–1182.PubMedGoogle Scholar
  172. Price LH, GA Ricaurte, JH Krystal and GR Heninger (1989) Neuroendocrine and mood responses to intravenous L-tryp-tophan in 3,4-methylenedioxymethamphetamine (MDMA) users. Preliminary observations.Arch. Gen. Psychiatry 46, 20–22.PubMedGoogle Scholar
  173. Puder KS, DV Kagan and JP Morgan (1988) Illicit metham-phetamine: analysis, synthesis, and availability.Am. J. Drug Alcohol Abuse 14, 463–473.PubMedGoogle Scholar
  174. Qiu J, MJ Whalen, P Lowenstein, G Fiskum, B Fahy, R Darwish, B Aarabi, J Yuan and MA Moskowitz (2002) Upregulation of the Fas receptor death-inducing signaling complex after traumatic brain injury in mice and humans.J. Neurosci. 22, 3504–3511.PubMedGoogle Scholar
  175. Raes E and AG Verstraete (2005) Usefulness of roadside urine drug screening in drivers suspected of driving under the influence of drugs (DUID).J Anal. Toxicol. 29, 632–636.PubMedGoogle Scholar
  176. Raivich G (2005) Like cops on the beat: the active role of resting microglia.Trends Neurosci. 28, 571–573.PubMedGoogle Scholar
  177. Ravagnan L, T Roumier and G Kroemer (2002) Mitochondria, the killer organelles and their weapons.J. Cell. Physiol. 192, 131–137.PubMedGoogle Scholar
  178. Reneman L, J Lavalaye, B Schmand, FA de Wolff, W van den Brink, GJ den Heeten and J Booij (2001) Cortical serotonin transporter density and verbal memory in individuals who stopped using 3,4-methylenedioxymethamphetamine (MDMA or “ecstasy”): preliminary findings.Arch. Gen. Psychiatry 58, 901–906.PubMedGoogle Scholar
  179. Ricaurte GA, CR Schuster and LS Seiden (1980) Long-term effects of repeated methylamphetamine administration on dopamine and serotonin neurons in the rat brain: a regional study.Brain Res. 193, 153–163.PubMedGoogle Scholar
  180. Ricaurte GA, LE De Lanney, SG Wiener, I Irwin and JW Langston (1988a) 5-Hydroxyindoleacetic acid in cerebro-spinal fluid reflects serotonergic damage induced by 3,4-methylenedioxymethamphetamine in CNS of non-human primates.Brain Res. 474, 359–363.Google Scholar
  181. Ricaurte GA, LS Forno, MA Wilson, LE De Lanney, I Irwin, ME Molliver and JW Langston (1988b) (+/-)3,4-Methylene dioxymethamphetamine selectively damages central serotonergic neurons in nonhuman primates.JAMA 260, 51–55.Google Scholar
  182. Ricaurte GA, KT Finnegan, I Irwin and JW Langston (1990) Aminergic metabolites in cerebrospinal fluid of humans previously exposed to MDMA: preliminary observations.Ann. NY. Acad. Sci. 600, 699–708; discussion 708-710.PubMedGoogle Scholar
  183. Ricaurte GA, UD McCann, Z Szabo and U Scheffel (2000) Toxicodynamics and long-term toxicity of the recreational drug, 3,4-methylenedioxymethamphetamine (MDMA, ‘Ecstasy’).Toxicol. Lett. 112–113, 143–146.PubMedGoogle Scholar
  184. Richard D (1995) Exercise and the neurobiological control of food intake and energy expenditure.Int. J. Obes. Relat. Metab. Disord. 19 Suppl. 4, S73–79.Google Scholar
  185. Rock RB, G Gekker, S Hu, WS Sheng, M Cheeran, JR Lokensgard and PK Peterson (2004) Role of microglia in central nervous system infections.Clin. Microbiol. Rev. 17, 942–964.PubMedGoogle Scholar
  186. Rogers RD, BJ Everitt, A Baldacchino, AJ Blackshaw, R Swainson, K Wynne, NB Baker, J Hunter, T Carthy, E Booker, M London, JF Deakin, BJ Sahakian and TW Robbins (1999) Dissociable deficits in the decision-making cognition of chronic amphetamine abusers, opiate abusers, patients with focal damage to prefrontal cortex, and trypto-phan-depleted normal volunteers: evidence for monoaminergic mechanisms.Neuropsychopharmacology 20, 322–339.PubMedGoogle Scholar
  187. Sabol KE, R Lew, JB Richards, GL Vosmer and LS Seiden (1996) Methylenedioxymethamphetamine-induced serotonin deficits are followed by partial recovery over a 52- week period. Part I: Synaptosomal uptake and tissue concentrations.J. Pharmacol. Exp. Ther. 276, 846–854.PubMedGoogle Scholar
  188. Salanova V and R Taubner (1984) Intracerebral haemorrhage and vasculitis secondary to amphetamine use.Postgrad. Med. J. 60, 429–430.PubMedGoogle Scholar
  189. Sanchez C (1989) The effects of dopamine D-1 and D-2 receptor agonists on body temperature in male mice.Eur. J. Pharmacol. 171, 201–206.PubMedGoogle Scholar
  190. Sanchez V, M Zeini, J Camarero, E O’Shea, L Bosca, AR Green and MI Colado (2003) The nNOS inhibitor, AR-R17477AR, prevents the loss of NF68 immunoreactivity induced by methamphetamine in the mouse striatum.J. Neurochem. 85, 515–524.PubMedGoogle Scholar
  191. Sapp E, KB Kegel, N Aronin, T Hashikawa, Y Uchiyama, K Tohyama, PG Bhide, JP Vonsattel and M DiFiglia (2001) Early and progressive accumulation of reactive microglia in the Huntington disease brain.J. Neuropathol. Exp. Neurol. 60, 161–172.PubMedGoogle Scholar
  192. Scanzello CR, G Hatzidimitriou, AL Martello, JL Katz and GA Ricaurte (1993) Serotonergic recovery after (+/-)3,4-(methylenedioxy) methamphetamine injury: observations in rats.J. Pharmacol. Exp. Ther. 264, 1484–1491.PubMedGoogle Scholar
  193. Scheffel U, C Steinert, SE Kim, MD Ehlers, JW Boja and MJ Kuhar (1996) Effect of dopaminergic drugs on thein vivo binding of [3H]WIN 35,428 to central dopamine transporters.Synapse 23, 61–69.PubMedGoogle Scholar
  194. Scheffel U, Z Szabo, WB Mathews, PA Finley, RF Dannals, HT Ravert, K Szabo, J Yuan and GA Ricaurte (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.PubMedGoogle Scholar
  195. Schmidt CJ (1987) Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine.J. Pharmacol. Exp. Ther. 240, 1–7.PubMedGoogle Scholar
  196. Schmidt CJ (1989) Acute and long-term neurochemical effects of methylenedioxymethamphetamine in the rat.NIDA Res. Monogr. 94, 179–195.PubMedGoogle Scholar
  197. Schmidt CJ and JH Kehne (1990) Neurotoxicity of MDMA: neurochemical effects. Ann.NY Acad. Sci. 600, 665–680; discussion 680-681.Google Scholar
  198. Schmidt CJ, L Wu and W Lovenberg (1986) Methylenediox ymethamphetamine: a potentially neurotoxic amphetamine analogue.Eur. J. Pharmacol. 124, 175–178.Google Scholar
  199. Schmidt CJ, JA Levin and W Lovenberg (1987)In vitro andin vivo neurochemical effects of methylenedioxymethamphetamine on striatal monoaminergic systems in the rat brain.Biochem. Pharmacol.36, 747–755.PubMedGoogle Scholar
  200. Schmidt CJ, CK Black and VL Taylor (1990) Antagonism of the neurotoxicity due to a single administration of methy-lenedioxymethamphetamine.Eur. J. Pharmacol. 181, 59–70.PubMedGoogle Scholar
  201. Schwartz K, A Weizman and M Rehavi (2006) The effect of psychostimulants on [3H]dopamine uptake and release in rat brain synaptic vesicles.J. Neural Transm. 113, 1347–1352.PubMedGoogle Scholar
  202. Seale TW, JM Carney, P Johnson and OM Rennert (1985) Inheritance of amphetamine-induced thermoregulatory responses in inbred mice.Pharmacol. Biochem. Behav. 23, 373–377.PubMedGoogle Scholar
  203. Seiden LS, KE Sabol and GA Ricaurte (1993) Amphetamine: effects on catecholamine systems and behavior.Annu. Rev. Pharmacol. Toxicol. 33, 639–677.PubMedGoogle Scholar
  204. Sekine Y, M Iyo, Y Ouchi, T Matsunaga, H Tsukada, H Okada, E Yoshikawa, M Futatsubashi, N Takei and N Mori (2001) Methamphetamine-related psychiatric symptoms and reduced brain dopamine transporters studied with PET.Am. J. Psychiatry 158, 1206–1214.PubMedGoogle Scholar
  205. Sekine Y, Y Minabe, Y Ouchi, N Takei, M Iyo, K Nakamura, K Suzuki, H Tsukada, H Okada, E Yoshikawa, M Futatsubashi and N Mori (2003) Association of dopamine transporter loss in the orbitofrontal and dorsolateral prefrontal cortices with methamphetamine-related psychiatric symptoms.Am. J. Psychiatry 160, 1699–1701.PubMedGoogle Scholar
  206. Sekine Y, Y Ouchi, N Takei, E Yoshikawa, K Nakamura, M Futatsubashi, H Okada, Y Minabe, K Suzuki, Y Iwata, KJ Tsuchiya, H Tsukada, M Iyo and N Mori (2006) Brain serotonin transporter density and aggression in abstinent meth-amphetamine abusers.Arch. Gen. Psychiatry 63, 90–100.PubMedGoogle Scholar
  207. Semple DM, KP Ebmeier, MF Glabus, RE O’Carroll and EC Johnstone (1999) Reducedin vivo binding to the serotonin transporter in the cerebral cortex of MDMA (‘ecstasy’) users.Br. J. Psychiatry 175, 63–69.PubMedGoogle Scholar
  208. Shankaran M and GA Gudelsky (1998) Effect of 3,4-meth-ylenedioxymethamphetamine (MDMA) on hippocampal dopamine and serotonin.Pharmacol. Biochem. Behav. 61, 361–366.PubMedGoogle Scholar
  209. Sheng P, C Cerruti, S Ali and JL Cadet (1996) Nitric oxide is a mediator of methamphetamine (METH)-induced neurotoxicity.In vitro evidence from primary cultures of mesencephalic cells.Ann. NYAcad. Sci. 801, 174–186.Google Scholar
  210. Silva OA and M Yonamine (2004) Drug abuse among workers in Brazilian regions.Rev. Saude Publica 38, 552–556.PubMedGoogle Scholar
  211. Simantov R and M Tauber (1997) The abused drug MDMA (ecstasy) induces programmed death of human serotonergic cells.FASEB J. 11, 141–146.PubMedGoogle Scholar
  212. Simon SL, C Domier, J Carnell, P Brethen, R Rawson and W Ling (2000) Cognitive impairment in individuals currently using methamphetamine.Am. J. Addict. 9, 222–231.PubMedGoogle Scholar
  213. Slikker W Jr, SF Ali, AC Scallet, CH Frith, GD Newport and JR Bailey (1988) Neurochemical and neurohistological alterations in the rat and monkey produced by orally administered methylenedioxymethamphetamine (MDMA).Toxicol. Appl. Pharmacol. 94, 448–457.PubMedGoogle Scholar
  214. Smith LM, LL LaGasse, C Derauf, P Grant, R Shah, A Arria, M Huestis, W Haning, A Strauss, SD Grotta, J Liu and BM Lester (2006) The infant development, environment, and lifestyle study: effects of prenatal methamphetamine exposure, polydrug exposure, and poverty on intrauterine growth.Pediatrics 118, 1149–1156.PubMedGoogle Scholar
  215. Sonsalla PK, WJ Nicklas and RE Heikkila (1989) Role for excitatory amino acids in methamphetamine-induced nigrostriatal dopaminergic toxicity.Science 243, 398–400.PubMedGoogle Scholar
  216. Sprague JE and DE Nichols (1995) Inhibition of MAO-B protects against MDMA-induced neurotoxicity in the striatum.Psychopharmacology (Berl.) 118, 357–359.Google Scholar
  217. Sprague JE, ML Banks, VJ Cook and EM Mills (2003) Hypothalamic-pituitary-thyroid axis and sympathetic nervous system involvement in hyperthermia induced by 3,4-methylenedioxymethamphetamine (ecstasy).J. Pharmacol. Exp. Ther. 305, 159–166.Google Scholar
  218. Sprague JE, P Moze, D Caden, DE Rusyniak, C Holmes, DS Goldstein and EM Mills (2005) Carvedilol reverses hyperthermia and attenuates rhabdomyolysis induced by 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) in an animal model.Crit. Care Med. 33, 1311–1316.PubMedGoogle Scholar
  219. Sriram K, DB Miller and JP O’Callaghan (2006) Minocycline attenuates microglial activation but fails to mitigate striatal dopaminergic neurotoxicity: role of tumor necrosis factor- alpha.J. Neurochem. 96, 706–718.PubMedGoogle Scholar
  220. Steentoft A, B Teige, P Holmgren, E Vuori, J Kristinsson, AC Hansen, G Ceder, G Wethe and D Rollmann (2006) Fatal poisoning in Nordic drug addicts in 2002.Forensic Sci. Int. 160, 148–156.PubMedGoogle Scholar
  221. Stewart VC, AJ Heslegrave, GC Brown, JB Clark and SJ Heales (2002) Nitric oxide-dependent damage to neuronal mitochondria involves the NMD A receptor.Eur. J. Neurosci. 15, 458–464.PubMedGoogle Scholar
  222. Stokes AH, TG Hastings and KE Vrana (1999) Cytotoxic and genotoxic potential of dopamine.J. Neurosci. Res. 55, 659–665.PubMedGoogle Scholar
  223. Stone DM, DC Stahl, GR Hanson and JW Gibb (1986) The effects of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) on mono-aminergic systems in the rat brain.Eur. J. Pharmacol. 128, 41–48.PubMedGoogle Scholar
  224. Stone DM, KM Merchant, GR Hanson and JW Gibb (1987) Immediate and long-term effects of 3,4-methylenedioxy-methamphetamine on serotonin pathways in brain of rat.Neuropharmacology 26, 1677–1683.PubMedGoogle Scholar
  225. Stumm G, J Schlegel, T Schafer, C Wurz, HD Mennel, JC Krieg and H Vedder (1999) Amphetamines induce apoptosis and regulation of bcl-x splice variants in neocortical neurons.FASEB J. 13, 1065–1072.PubMedGoogle Scholar
  226. Sulzer D, TK Chen, YY Lau, H Kristensen, S Rayport and A Ewing (1995) Amphetamine redistributes dopamine from synaptic vesicles to the cytosol and promotes reverse transport.J. Neurosci. 15, 4102–4108.PubMedGoogle Scholar
  227. Taraska T and KT Finnegan (1997) Nitric oxide and the neurotoxic effects of methamphetamine and 3,4-methylenedioxy-methamphetamine.J. Pharmacol. Exp. Ther. 280, 941–947.PubMedGoogle Scholar
  228. Thiriet N, B Ladenheim, MT McCoy and JL Cadet (2002) Analysis of ecstasy (MDMA)-induced transcriptional responses in the rat cortex.FASEB J. 16, 1887–1894.PubMedGoogle Scholar
  229. Thiriet N, X Deng, M Solinas, B Ladenheim, W Curtis, SR Goldberg, RD Palmiter and JL Cadet (2005) Neuropeptide Y protects against methamphetamine-induced neuronal apoptosis in the mouse striatum.J. Neurosci. 25, 5273–5279.PubMedGoogle Scholar
  230. Thomas DM and DM Kuhn (2005) MK-801 and dextro-methorphan block microglial activation and protect against methamphetamine-induced neurotoxicity.Brain Res. 1050, 190–198.PubMedGoogle Scholar
  231. Thomas DM, J Dowgiert, TJ Geddes, D Francescutti-Verbeem, X Liu and DM Kuhn (2004) Microglial activation is a pharmacologically specific marker for the neurotoxic amphetamines.Neurosci. Lett. 367, 349–354.PubMedGoogle Scholar
  232. Verma A and SK Kulkarni (1993) Differential role of dopamine receptor subtypes in thermoregulation and stereotypic behavior in naive and reserpinized rats.Arch. Int. Pharmacodyn. Ther. 324, 17–32.PubMedGoogle Scholar
  233. Volkow ND, L Chang, GJ Wang, JS Fowler, D Franceschi, MJ Sedler, SJ Gatley, R Hitzemann, YS Ding, C Wong and J Logan (2001a) Higher cortical and lower subcortical metabolism in detoxified methamphetamine abusers.Am. J. Psychiatry 158, 383–389.Google Scholar
  234. Volkow ND, L Chang, GJ Wang, JS Fowler, M Leonido-Yee, D Franceschi, MJ Sedler, SJ Gatley, R Hitzemann, YS Ding, J Logan, C Wong and EN Miller (2001b) Association of dopamine transporter reduction with psychomotor impairment in methamphetamine abusers.Am. J. Psychiatry 158, 377–382.Google Scholar
  235. Wagner GC, GA Ricaurte, CE Johanson, CR Schuster and LS Seiden (1980a) Amphetamine induces depletion of dopamine and loss of dopamine uptake sites in caudate.Neurology 30, 547–550.Google Scholar
  236. Wagner GC, GA Ricaurte, LS Seiden, CR Schuster, RJ Miller and J Westley (1980b) Long-lasting depletions of striatal dopamine and loss of dopamine uptake sites following repeated administration of methamphetamine.Brain Res. 181, 151–160.Google Scholar
  237. Wagner GC, RM Carelli and MF Jarvis (1985) Pretreatment with ascorbic acid attenuates the neurotoxic effects of methamphetamine in rats.Res. Commun. Chem. Pathol. Pharmacol. 47, 221–228.PubMedGoogle Scholar
  238. Wan FJ, HC Lin, YS Lin and CJ Tseng (2000) Intra-striatal infusion of D-amphetamine induces hydroxyl radical formation: inhibition by MK-801 pretreatment.Neuropharmacology 39, 419–426.PubMedGoogle Scholar
  239. Werner S and C Alzheimer (2006) Roles of activin in tissue repair, fibrosis, and inflammatory disease.Cytokine Growth Factor Rev. 17, 157–171.PubMedGoogle Scholar
  240. White SR, T Obradovic, KM Imel and MJ Wheaton (1996) The effects of methylenedioxymethamphetamine (MDMA, “ecstasy”) on monoaminergic neurotransmission in the central nervous system.Prog. Neurobiol. 49, 455–479.PubMedGoogle Scholar
  241. Wieloch T and K Nikolich (2006) Mechanisms of neural plasticity following brain injury.Curr. Opin. Neurobiol. 16, 258–264.PubMedGoogle Scholar
  242. Wilson JM, KS Kalasinsky, AI Levey, C Bergeron, G Reiber, RM Anthony, GA Schmunk, K Shannak, JW Haycock and SJ Kish (1996) Striatal dopamine nerve terminal markers in human, chronic methamphetamine users.Nat. Med. 2, 699–703.PubMedGoogle Scholar
  243. Wylie FM, H Torrance, A Seymour, S Buttress and JS Oliver (2005) Drugs in oral fluid. Part II. Investigation of drugs in drivers.Forensic Sci. Int. 150, 199–204.PubMedGoogle Scholar
  244. Xiang Z, V Haroutunian, L Ho, D Purohit and GM Pasinetti (2006) Microglia activation in the brain as inflammatory biomarker of Alzheimer’s disease neuropathology and clinical dementia.Dis. Markers 22, 95–102.PubMedGoogle Scholar
  245. Yeh SY and FL Hsu (1991) The neurochemical and stimulatory effects of putative metabolites of 3,4-methylene-dioxyamphetamine and 3,4-methylenedioxymethamphet-amine in rats.Pharmacol. Biochem. Behav. 39, 787–790.PubMedGoogle Scholar
  246. Yui K, K Goto, S Ikemoto, T Ishiguro, B Angrist, GE Duncan, BB Sheitman, JA Lieberman, SH Bracha and SF Ali (1999) Neurobiological basis of relapse prediction in stimulant-induced psychosis and schizophrenia: the role of sensitization.Mol. Psychiatry 4, 512–523.PubMedGoogle Scholar
  247. Zafar KS, D Siegel and D Ross (2006) A potential role for cyclized quinones derived from dopamine, DOPA, and 3,4-dihydroxyphenylacetic acid in proteasomal inhibition.Mol. Pharmacol. 70, 1079–1086.PubMedGoogle Scholar
  248. Zarrindast MR and SA Tabatabai (1992) Involvement of dopamine receptor subtypes in mouse thermoregulation.Psychopharmacology (Berl.) 107, 341–346.Google Scholar
  249. Zinszner H, M Kuroda, X Wang, N Batchvarova, RT Lightfoot, H Remotti, JL Stevens and D Ron (1998) CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum.Genes Dev. 12, 982–995.PubMedGoogle Scholar

Copyright information

© Springer 2007

Authors and Affiliations

  • Jean Lud Cadet
    • 1
  • Irina N. Krasnova
    • 1
  • Subramaniam Jayanthi
    • 1
  • Johnalyn Lyles
    • 1
  1. 1.Molecular Neuropsychiatry Branch, DHHS/NIH/NIDAIntramural Research ProgramBaltimoreUSA

Personalised recommendations