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Neuropharmacology and Neurotoxicity of 3,4-Methylenedioxymethamphetamine

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Drugs of Abuse

Part of the book series: Methods In Molecular Medicine™ ((MIMM,volume 79))

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Abstract

With the continuing and increasing popularity of the amphetamine analog 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) as a drug of abuse, concern also has increased regarding the long-term psychological and neurochemical effects of this drug. The acute psychological effects of MDMA include a mild sense of euphoria and sense of well being and increased ability to interact with others (1) which contribute to the drug’s popularity. Recent studies in laboratory animals and humans indicate that repeated exposure to MDMA elicits long-term changes in neurochemistry and behavior that are viewed as resulting from a selective neurotoxicity of 5-hydroxytryptamine (5-HT)-containing axon terminals.

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References

  1. Parrott, A. C. (2002) Recreational Ecstasy/MDMA, the serotonin syndrome, and serotonergic neurotoxicity. Pharmacol. Biochem. Behav. 71, 837–844.

    Article  PubMed  CAS  Google Scholar 

  2. Nichols, D. E., Lloyd, D. H., Hoffman, A. J., Nichols, M. D., and Yim, G. K. (1982) Effects of certain hallucinogenic amphetamine analogues on the release of [3H]serotonin from rat brain synaptoxomes. J. Med. Chem. 25, 530–535.

    Article  PubMed  CAS  Google Scholar 

  3. Johnson, M. P., Hoffman, A. J., and Nichols, D. E. (1986) Effects of the enantiomers of MDA, MDMA and related analogues on [3H]serotonin and [3H]dopamine release from superfused rat brain slices. Eur. J. Pharmacol. 132, 269–276.

    Article  PubMed  CAS  Google Scholar 

  4. Gough, B., Ali, S. F., Slikker, W., Jr., and Holson, R. R. (1991) Acute effects of 3,4-methylenedioxymethamphetamine (MDMA) on monoamines in rat caudate. Pharmacol. Biochem. Behav. 39, 619–623.

    Article  PubMed  CAS  Google Scholar 

  5. Gudelsky, G. A. and Nash, J. F. (1996) Carrier-mediated release of serotonin by 3,4-methylenedioxymethamphetamine: implications for serotonin-dopamine interactions. J. Neurochem. 66, 243–249.

    Article  PubMed  CAS  Google Scholar 

  6. Rudnick, G. and Wall, S. C. (1992) The molecular mechanism of “ecstasy” [3,4-methylenedioxymethamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release. Proc. Natl. Acad. Sci. USA 89, 1817–1821.

    Article  PubMed  CAS  Google Scholar 

  7. Yamamoto, B. K. and Spanos, L. J. (1988) The acute effects of methylenedioxymethamphetamine on dopamine release in the awake-behaving rat. Eur. J. Pharmacol. 148, 195–203.

    Article  PubMed  CAS  Google Scholar 

  8. Nash, J. F. and Nichols, D. E. (1991) Microdialysis studies on 3,4-methylenedioxyamphetamine and structurally related analogues. Eur J.Pharmacol. 200, 53–58.

    Article  PubMed  CAS  Google Scholar 

  9. Nash, J. F. and Brodkin, J. (1991) Microdialysis studies on 3,4-methylenedioxymethamphetamine-induced dopamine release: effect of dopamine uptake inhibitors. J. Pharmacol. Exp. Ther. 259, 820–825.

    PubMed  CAS  Google Scholar 

  10. Yamamoto, B. K., Nash, J. F., and Gudelsky, G. A. (1995) Modulation of methylenedioxymethamphetamine-induced striatal dopamine release by the interaction between serotonin and γ-aminobutyric acid in the substantia nigra. J. Pharmacol. Exp. Ther. 273, 1063–1070.

    PubMed  CAS  Google Scholar 

  11. Nash, J. F. (1990) Ketanserin pretreatment attenuates MDMA-induced dopamine release in the striatum as measured by in vivo microdialysis. Life Sci. 47, 2401–2408.

    Article  PubMed  CAS  Google Scholar 

  12. Gudelsky, G. A., Yamamoto, B. K., and Nash, J. F. (1994) Potentiation of 3,4-methylenedioxymethamphetamine-induced dopamine release and serotonin neurotoxicity by 5-HT2 agonists. Eur. J. Pharmacol. 264, 325–330.

    Article  PubMed  CAS  Google Scholar 

  13. 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.

    Article  PubMed  CAS  Google Scholar 

  14. Fisher, H. S., Zerning, G., Schatz, D. S., Humpel, C., and Saria, A. (2000) MDMA (Ecstasy) enhances basal acetylcholine release in brain slices of the rat striatum. Eur. J. Neurosci. 12, 1385–1390.

    Article  Google Scholar 

  15. Acquas, E., Marrocu, P., Pisanu, A., et al. (2001) Intravenous administration of ecstasy (3,4-methylenedioxymethamphetamine) enhances cortical and striatal acetylcholine release in vivo. Eur. J. Pharmacol. 418, 207–211.

    Article  PubMed  CAS  Google Scholar 

  16. Nair, S. and Gudelsky, G. A. (2002) MDMA enhances acetylcholine release in the prefrontal cortex and hippocampus of the rat. Soc. Neurosci. Abstr. No. 809.17.

    Google Scholar 

  17. Nash, J. F., Jr., Meltzer, H. Y., and Gudelsky, G. A. (1988) Elevation of serum prolactin and corticosterone concentrations in the rat after the administration of 3,4-methylenedioxymethamphetamine. J. Pharmacol. Exp. Ther. 245, 873–879.

    PubMed  CAS  Google Scholar 

  18. Schmidt, C. J., Black, C. K., Abbate, G. M., and Taylor V. L. (1990) Methylenedioxymethamphetamine-induced hyperthermia and neurotoxicity are independently mediated by 5-HT2 receptors. Brain Res. 529, 85–90.

    Article  PubMed  CAS  Google Scholar 

  19. Spanos, L. J. and Yamamoto, B. K. (1989) Acute and subchronic effects of methylenedioxymethamphetamine [(±)MDMA] on locomotion and serotonin syndrome behavior in the rat. Pharmacol. Biochem. Behav. 32, 835–840.

    Article  PubMed  CAS  Google Scholar 

  20. Shankaran, M. and Gudelsky, G. A. (1999) A neruotoxic regimen of MDMA suppresses behavioral, thermal and neurochemical responses to subsequent MDMA administration. Psychopharmacology 147, 66–72.

    Article  PubMed  CAS  Google Scholar 

  21. McCreary, A. C., Bankson, M. G., and Cunningham, K. A. (1999) Pharmacological studies of the acute and chronic effects of (+)-3,4-methylenedioxymethamphetamine on locomotor activity: role of 5-hydroxytryptamine1A and 5-hydroxytryptamine1B/1D receptors. J. Pharmacol. Exp. Ther. 290, 965–973.

    PubMed  CAS  Google Scholar 

  22. Morley, K. C. and McGregor, I. S. (2000) (±)-3,4-Methylenedioxymethamphetamine (MDMA, ‘Ecstasy’) increases social interaction in rats. Eur. J. Pharmacol. 408, 41–49.

    Article  PubMed  CAS  Google Scholar 

  23. Schmidt, C. J. (1987) Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. J. Pharmacol. Exp. Ther. 240, 1–7.

    PubMed  CAS  Google Scholar 

  24. Ricaurte, G. A. Forno, L., Wilson, M. A., et al. (1988) (+)-3,4-Methylenedioxymethamphetamine selectively damages central serotonergic neurons in nonhuman primates. JAMA 260, 51–55.

    Article  PubMed  CAS  Google Scholar 

  25. Battaglia, G., Yeh, S. Y., O’Hearn, E., Molliver, M. E., Kuhar, M., and De Souza, E. B. (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, 911–921.

    PubMed  CAS  Google Scholar 

  26. Stone, D. M., Stahl, D., Hanson, G. R., and Gibb, J. W. (1986) The effects of 3,4-methylenedioxymethamphetamine (MDMA) on monoaminergic systems in rat brain. Eur. J. Pharmacol. 128, 41–49.

    Article  PubMed  CAS  Google Scholar 

  27. O’Hearn, E., Battaglia, G., De Souza, E. B., Kuhar, M. J., and Molliver, M. E. (1988) Methylenedioxyamphetamine (MDA) and methylenedioxy-methamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity. J. Neurosci. 8, 2788–2803.

    Google Scholar 

  28. Logan, B. J., Laverty, R., Sanderson, W. D., and Yee, Y. B. (1988) Differences between rats and mice in MDMA (methylenedioxy-methylamphetamine) neurotoxicity. Eur. J. Pharmacol. 152, 227–234.

    Article  PubMed  CAS  Google Scholar 

  29. Miller, D. B. and O’Callaghan, J. P. (1994) Environment, drug and stress-induced alterations in body temperature affect the neurotoxicity of substituted amphetamines in the C57B1/6J mouse. J. Pharmacol. Exp. Ther. 270, 752–760.

    PubMed  CAS  Google Scholar 

  30. McCann, U., Szabo, Z., Scheffel, U., Dannais, R., 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.

    Article  PubMed  CAS  Google Scholar 

  31. Reneman, L., Lavalaye, J., Schmand, B., et al. (2001) Cortical serotonin transport density and verbal memory in individuals who stopped using 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy). Arch. Gen. Psychiatry 58, 901–906.

    Article  PubMed  CAS  Google Scholar 

  32. Sabol, K. E., Lew, R., Richards, J. B., Vosmer, G. L., and Seiden, L. S. (1996) Methylenedioxymethamphetamine-induced serotonin deficits are followed by partial recovery over a 51-week period. Part I: Synaptosomal uptake and tissue concentrations. J. Pharmacol. Exp. Ther. 276, 846–854.

    PubMed  CAS  Google Scholar 

  33. Lew, R., Sabol, K. E., Chou, C., Vosmer, G. L., Richards, J., and Seiden, L. S. (1996) Methylenedioxymethamphetamine-induced serotonin deficits are followed by partial recovery over a 52-week period. Part II: Radioligand binding and autoradiography studies. J. Pharmacol. Exp. Ther. 276, 855–865.

    PubMed  CAS  Google Scholar 

  34. Fischer, C., Hatzidimitriou, G., Wios, 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. Neurosci. 15, 5476–5485.

    PubMed  CAS  Google Scholar 

  35. Commins, D. L., Vosmer, G., Virius, R., Woolverton, W. L., Schuster, C. R., and Seiden, L. S. (1987) Biochemical and histological evidence that methylenedioxymethamphetamine (MDMA) is toxic to neurons in the rat brain. J. Pharmacol. Exp. Ther. 241, 338–344.

    PubMed  CAS  Google Scholar 

  36. Scallet, A. C., Lipe, G. W., Ali, S. F., Holson, R. R., Frith, C. H., and Slikker, W., Jr. (1988) Neuropathological evaluation by combined immunohistochemistry and degeneration-specific methods: application of methylenedioxymethamphetamine. Neurotoxicology 9, 529–538.

    PubMed  CAS  Google Scholar 

  37. O’Callaghan, J. P. and Miller, D. B. (1993) Quantification of reactive gliosis as an approach to neurotoxicity, in Assessing Neurotoxicity of Drugs of Abuse (Erinoff, L., ed.), NIDA Monograph 136, pp. 188–212.

    Google Scholar 

  38. Callahan, B. T., Cord, B. J., and Ricaurte, G. A. (2001) Long-term impairment of anterograde axonal transport along fiber projections originating in the rostral raphe nuclei after treatment with fenfluramine or methylenedioxymethamphetamine. Synapse 40, 113–121.

    Article  PubMed  CAS  Google Scholar 

  39. Gudelsky, G. A., Wallace, T. L., Vorhees, C. V., and Zemlan, F. P. (2001) Methamphetamine enhances the cleavage of the cytoskeletal protein tau in the striatum and hippocampus of the rat. Soc. Neurosci. Abstr. 358.6.

    Google Scholar 

  40. Schmidt, C. J., Black, C. K., Abbate, G. M., and Taylor, V. L. (1990) Antagonism of the neurotoxicity due to a single administration of methylenedioxymethamphetamine. Eur. J. Pharmaocol. 181, 59–70.

    Article  CAS  Google Scholar 

  41. Aguirre, N., Barrionuevo, M., Lasheras, B., and Del Río, J. (1998) The role of dopaminergic systems in the perinatal sensitivity to 3,4-methylenedioxymethamphetamine-induced neurotoxicity in rats. J. Pharmacol. Exp. Ther. 286, 1159–1165.

    PubMed  CAS  Google Scholar 

  42. Stone, D. M., Johnson, M., Hanson, G. R., and Gibb, J. W. (1988) Role of endogenous dopamine in the central serotonergic deficits induced by 3,4-methylenedioxymethamphetamine. J. Pharmacol. Exp. Ther. 247, 79–87.

    PubMed  CAS  Google Scholar 

  43. Shankaran, M., Yamamoto, B. K., and Gudelsky, G. (1999) Mazindol attenuates the 3,4-methylenedioxymethamphetamine-induced formation of hydroxyl radicals and long-term depletion of serotonin in the striatum. J. Neurochem. 72, 2516–2522.

    Article  PubMed  CAS  Google Scholar 

  44. Kanthasamy, A. and Nichols, D. E. (2002) Unilateral injection of dopamine transporter antisense oligonucleotide into the substantia nigra protects against MDMA-induced serotonergic deficits in the ipsilateral striatum. Soc. Neurosci. Abstr., No. 445.18.

    Google Scholar 

  45. Schmidt, C. J., Taylor, V. L., Abbate, G. M., and Nieduzak, T. R. (1991) 5-HT2 antagonists stereoselectively prevent the neurotoxicity of 3,4-methylenedioxymethamphetamine by blocking the acute stimulation of dopamine synthesis: reversal by l-dopa. J. Pharmacol. Exp. Ther. 256, 230–235.

    PubMed  CAS  Google Scholar 

  46. Michel, P. P. and Hefti, F. (1990) Toxicity of 6-hydroxydopamine and dopamine for dopaminergic neurons in culture. J. Neurosci. Res. 26, 428–435.

    Article  PubMed  CAS  Google Scholar 

  47. Filloux, F. and Townsend, J. J. (1993) Pre-and postsynaptic neurotoxic effects of dopamine demonstrated by intrastriatal injection. Exp. Neurol. 119, 79–88.

    Article  PubMed  CAS  Google Scholar 

  48. Sprague, J. E., Everman, S. L., and Nichols, D. E. (1998) An integrated hypothesis for the serotonergic axonal loss induced by 3,4-methylene-dioxymethamphetamine. Neurotoxicology 19, 427–442.

    PubMed  CAS  Google Scholar 

  49. Johnson, M. P. and Nichols, D. E. (1991) Combined administration of a non-neurotoxic 3,4-methylenedioxymethamphetamine analogue with amphetamine produces serotonin neurotoxicity in rats. Neuropharmacology 30, 819–822.

    Article  PubMed  CAS  Google Scholar 

  50. Schmidt, C. J. and Kehne, J. H. (1990) Neurotoxicity of MDMA: neurochemical effects. Ann. NY Acad. Sci. 600, 665–680.

    Article  PubMed  CAS  Google Scholar 

  51. Shankaran, M., Yamamoto, B. K., and Gudelsky, G. A. (1999) Involvement of the serotonin transporter in the formation of hydroxyl radicals induced by 3,4-methylenedioxymethamphetamine. Eur. J. Pharmacol. 385, 103–110.

    Article  PubMed  CAS  Google Scholar 

  52. Kramer, H. K., Poblete, J. C., and Azmitia, E. C. (1997) Activation of protein kinase C (PKC) by 3,4-methylenedioxymethamphetamine (MDMA) occurs through the stimulation of serotonin receptors and transporter. Neuropsychopharmacology 17, 117–129.

    Article  PubMed  CAS  Google Scholar 

  53. Molliver, M. E., O’Hearn, E., Battaglia, G., and DeSouza, E. B. (1986) Direct intracerebral administration of MDA and MDMA does not produce serotonin neurotoxicity. Soc. Neurosci. Abstr. 12, 1234.

    Google Scholar 

  54. Paris, J. M. and Cunningham, K. A. (1991) Lack of serotonin neurotoxicity after intraraphe microinjection of (+)-3,4-methylenedioxymethamphetamine (MDMA). Brain Res. Bull. 28, 115–119.

    Article  Google Scholar 

  55. Nixdorf, W. L., Burrows, K. B., Gudelsky, G. A., and Yamamoto, B. K. (2001) Enhancement of 3.4-methylenedioxymethamphetamine neurotoxicity by the energy inhibitor malonate. J. Neurochem. 77, 647–654.

    Article  PubMed  CAS  Google Scholar 

  56. Esteban, B., O’Shea, E., and Camarero, J. (2001) 3,4-Methylenedioxymethamphetamine induces monoamine release, but not toxicity, when administered centrally at a concentration occurring following a peripherally injected neurotoxic dose. Psychopharmacology 154, 251–260.

    Article  PubMed  CAS  Google Scholar 

  57. Miller, R. T., Lau, S. S., and Monks, T. J. (1997) 2,4-bis-(Glutathion-S-yl)-α-methyldopamine, a putative metabolite of 3,4-methylenedioxy-methamphetamine, decreases brain serotonin concentrations. Eur. J. Pharmacol. 323, 173–180.

    Article  PubMed  CAS  Google Scholar 

  58. Bai, F., Jones, D. C., Lau, S. S., and Monks, T. J. (2001) Serotonergic neurotoxicity of 3,4-(±)-methylenedioxyamphetamine and 3,4-(±)-methylendioxymethamphetamine (Ecstasy) is potentiated by inhibition of γ-glutamyl transpeptidase. Chem. Res. Toxicol. 14, 863–870.

    Article  PubMed  CAS  Google Scholar 

  59. Gudelsky, G. A. (1996) Effect of ascorbate and cysteine on the 3-4-methylenedioxymethamphetamine-induced depletion of brain serotonin. J. Neural Transm. 103, 1397–1404.

    Article  PubMed  CAS  Google Scholar 

  60. Malberg, J. E. and Seiden, L. S. (1998) Small changes in ambient temperature cause large changes in 3,4-methylenedioxy-methamphetamine (MDMA)-induced serotonin neurotoxicity and core body temperature in the rat. J. Neurosci. 18, 5086–5094.

    PubMed  CAS  Google Scholar 

  61. Darvesh, A. S., Shankaran, M., and Gudelsky, G. (2002) 3,4-methylenedioxymethamphetamine produces glycogenolysis and increases the extracellular concentration of glucose in the rat brain. J. Pharmacol. Exp. Ther. 300, 138–144.

    Article  Google Scholar 

  62. Broening, H. W., Bowyer, J. F., and Slikker, W. Jr. (1995) Age-dependent sensitivity of rats to the long-term effects of the serotonergic neurotoxicant (±)-3,4-methylenedioxymethamphetamine (MDMA) correlates with the magnitude of the MDMA-induced thermal response. J. Pharmacol. Exp. Ther. 275, 325–333.

    PubMed  CAS  Google Scholar 

  63. Farfel, G. M. and Seiden, L. S. (1995) Role of hyperthermia in the mechanism of protection against serotonergic toxicity. I. Experiments using 3,4-methylenedioxymethamphetamine, dixolcipine, CGS 19755 and NBQX. J. Pharmacol. Exp. Ther. 272, 860–867.

    PubMed  CAS  Google Scholar 

  64. Malberg, J. E., Sabol, K. E., and Seiden, L. S. (1996) Co-administration of MDMA with drugs that protect against MDMA neurotoxicity produces different effects on body temperature in the rat. J. Pharamcol. Exp. Ther. 278, 258–267.

    CAS  Google Scholar 

  65. Colado, M. I., O’Shea, E., Granados, R., Murray, T. K., and Green, A. R. (1997) In vivo evidence for free radical involvement in the degeneration of rat brain 5-HT following administration of MDMA (‘ecstasy’) and p-chloramphetamine but not the degeneration following fenfluramine. Br. J. Pharmacol. 121, 889–900.

    Article  PubMed  CAS  Google Scholar 

  66. Colado, M. I., O’Shea, E., Granados, R., Esteban, B., Martin, A. B., and Green, A. R. (1999) Studies on the role of dopamine in the degeneration of 5-HT nerve endings in the brain of Dark Agouti rats following 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) administration. Br. J. Pharmacol. 126, 911–924.

    Article  PubMed  CAS  Google Scholar 

  67. Cadet, J. L., Ladenheim, B, Baum, I., Carlson, E., and Epstein, C. (1994) CuZn-superoxide dismutase (CuZnSOD) transgenic mice show resistance to the lethal effects of methylenedioxyamphetamine (MDA) and of methylenedioxymethamphetamine (MDMA). Brain Res. 655, 259–262.

    Article  PubMed  CAS  Google Scholar 

  68. Colado, M. I., Camarero, J., Mechan, A. O., et al. (2001) A study of the mechanisms involved in the neurotoxic action of 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) on dopamine neurones in mouse brain. Br. J. Pharmacol. 134, 1711–1723.

    Article  PubMed  CAS  Google Scholar 

  69. Taraska, T. and Finnegan, K. T. (1997) Nitric oxide and the neurotoxic effects of methamphetamine and 3,4-methylenedioxymethamphetamine. J. Pharmacol. Exp. Ther. 280, 941–947.

    PubMed  CAS  Google Scholar 

  70. Zheng, Y. and Laverty, R. (1998) Role of brain nitric oxide in (±)3,4-methylenedioxymethamphetamine (MDMA)-induced neurotoxicity in rats. Brain Res. 795, 257–263.

    Article  PubMed  CAS  Google Scholar 

  71. Nash, J. F. and Yamamoto, B. K. (1992) Methamphetamine neurotoxicity and striatal glutamate release: comparison to 3,4-methylenedioxymethamphetamine. Brain Res. 581, 237–243.

    Article  PubMed  CAS  Google Scholar 

  72. Burrows, K. B., Gudelsky, G. A., and Yamamoto, B. K. (2000) Rapid and transient inhibition of mitochondrial function following methamphetamine or 3,4-methylenedioxymethamphetamine administration. Eur. J. Pharmacol. 398, 11–18.

    Article  PubMed  CAS  Google Scholar 

  73. Sprague, J. E. and Nichols, D. E. (1995) The monoamine oxidase-B inhibitor l-deprenyl protects against 3,4-methylenedioxy-methamphetamine-induced lipid peroxidation and long-term serotonergic deficits. J. Pharmacol. Exp. Ther. 273, 667–673.

    PubMed  CAS  Google Scholar 

  74. Colado, M. I., O’Shea, E., Ados, R., Misra, A., Murray, T. K., and Green, A. R. (1997) A study of the neurotoxic effect of MDMA (‘ecstasy’) on 5-HT neurones in the brains of mothers and neonates following administration of the drug during pregnancy. Br. J. Pharmacol. 121, 827–833.

    Article  PubMed  CAS  Google Scholar 

  75. Shankaran, M., Yamamoto, B. K., and Gudelsky, G. A. (2001) Ascorbic acid prevents 3,4-methylenedioxymethamphetamine (MDMA)-induced hydroxyl radical formation and the behavioral and neurochemical consequences of the depletion of brain 5-HT. Synapse 40, 55–64.

    Article  PubMed  CAS  Google Scholar 

  76. Colado, M. I. and Green, A. R. (1995) The spin trap reagent α-phenyl-N-tert-butyl nitrone prevents ‘ecstasy’-induced neurodegeneration of 5-hydroxytryptamine neurons. Eur. J. Pharmacol. 280, 343–346.

    Article  PubMed  CAS  Google Scholar 

  77. Yeh, S. Y. (1999) N-tert-Butyl-alpha-phenylnitrone protects against 3,4-methylenedioxymethamphetamine-induced depletion of serotonin in rats. Synapse 31, 169–177.

    PubMed  CAS  Google Scholar 

  78. Chan, P., Di Monte, D., Luo, J. J., DeLaney, L. E., Irwin, I., and Langston, J. W. (1994) Rapid ATP loss caused by methamphetamine in the mouse striatum: relationship between energy impairment and dopaminergic neuroxicity. J. Neurochem. 62, 2484–2487.

    Article  PubMed  CAS  Google Scholar 

  79. Stephans, S. E., Whittingham, T. S., Douglas, A. J., Lust, W. D., and Yamamoto, B. K. (1998) Substrates of energy metabolism attenuate methamphetamine-induced neurotoxicity in striatum. J. Neurochem. 71, 613–621.

    Article  PubMed  CAS  Google Scholar 

  80. Huang, N. K., Wan, F. J., Tseng, C. J., and Tung, C. S. (1997) Nicotinamide attenuates methamphetamine-induced striatal dopamine depletion in rats. NeuroReport 8, 1883–1885.

    Article  PubMed  CAS  Google Scholar 

  81. Burrows, K. B., Nixdorf, W. L., and Yamamoto, B. K. (2000) Central administration of methamphetamine synergizes with metabolic inhibition to deplete striatal monoamines. J. Pharmacol. Exp. Ther. 292, 853–860.

    PubMed  CAS  Google Scholar 

  82. Albers, D. S., Zeevalk, G., and Sonsalla, P. K. (1996) Damage to dopaminergic nerve terminals in mice by combined treatment of intrastriatal malonate with systemic methamphetamine or MPTP. Brain Res. 718, 217–220.

    Article  PubMed  CAS  Google Scholar 

  83. Huether, G., Zhou, D., and Rüther, E. (1997) Causes and consequences of the loss of serotonergic presynapses elicited by the consumption of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) and its congeners. J. Neural Transm. 104, 771–794.

    Article  PubMed  CAS  Google Scholar 

  84. Poblete, J. C. and Azmitia, E. C. (1995) Activation of glycogen phosphorylase by serotonin and 3,4-methylenedioxymethamphetamine in astroglial-rich primary cultures: involvement of the 5-HT2A receptor. Brain Res. 680, 9–15.

    Article  PubMed  CAS  Google Scholar 

  85. Series, H. G., Masurier, M., Gartside, S., Franklin, M., and Sharp, T. (1995) Behavioral and neuroendocrine responses to d-fenfluramine in rats treated with neurotoxic amphetamines. J. Psychopharmacol. 9, 214–219.

    Article  CAS  Google Scholar 

  86. Bauman, M. H., Ayestas, M., and Rothman, R. B. (1998) Functional consequences of central serotonin depletion produced by repeated fenfluramine administration to rats. J. Neurosci. 18, 9069–9077.

    Google Scholar 

  87. Poland, R. E., Lutchmansingh, P., McCracken, J. T., et al. (1997) Abnormal ACTH and prolactin responses to fenfluramine in rats exposed to single and multiple doses of MDMA. Psychopharmacology 131, 411–419.

    Article  PubMed  CAS  Google Scholar 

  88. Gartside, S., McQuade, R., and Sharp, T. (1996) Effects of repeated administration of 3,4-methylenedioxymethamphetamine on 5-hydroxytryptamine neuronal activity and release in the rat brain in vivo. J. Pharmacol. Exp. Ther. 279, 277–283.

    PubMed  CAS  Google Scholar 

  89. Aguirre, N., Frechilla, D., García-Osta, A., Lasheras, B., and Del Río, J. (1997) Differential regulation by methylenedioxymethamphetamine of 5-hydroxytryptamine1A receptor density and mRNA expression in rat hippocampus, frontal cortex, and brainstem: the role of corticosteroids. J. Neurochem. 68, 1099–1105.

    Article  PubMed  CAS  Google Scholar 

  90. Aguirre, N., Ballaz, S., Lasheras, B., and Del Río, J. (1998) MDMA (‘Ecstasy’) enhances 5-HT1A receptor density and 8-OH-DPAT-induced hypothermia: blockade by drugs preventing 5-hydroxytryptamine depletion. Eur. J. Pharmacol. 346, 181–188.

    Article  PubMed  CAS  Google Scholar 

  91. Wallace, T. L., Gudelsky, G., and Vorhees, C. V. (2001) Alterations in diurnal and nocturnal locomotor activity in rats treated with a monoamine-depleting regimen of methamphetamine or 3,4-methylenedioxymethamphetamine. Psychopharmacology 153, 321–326.

    Article  PubMed  CAS  Google Scholar 

  92. Dafters, R. I. and Lynch, E. (1998) Persistent loss of thermoregulation in the rat induced by 3,4-methylenedioxymethamphetamine (MDMA or “Ecstasy”) but not by fenfluramine. Psychopharmacology 138, 207–212.

    Article  PubMed  CAS  Google Scholar 

  93. Mechan, A. O., O’Shea, E., Elliott, J. M., Colado, M. I., and Green, A. R. (2001) A neurotoxic dose of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) to rats results in a long term defect in thermoregulation. Psychopharmacology 155, 413–418.

    Article  PubMed  CAS  Google Scholar 

  94. Matuszewich, L., Filon, M. E., Finn, D. A., and Yamamoto, B. K. (2002) Altered forebrain neurotransmitter responses to immobilization stress following 3,4-methylenedioxymethamphetamine. Neuroscience 110, 41–48.

    Article  PubMed  CAS  Google Scholar 

  95. Jones, B. E. (2000) Basic mechanisms of sleep-wake state, in Principles and Practice of Sleep Medicine, 3rd ed. (Kryger, M. H., Roth, T., and Dement, W. C., eds.), W. B. Saunders, Philadelphia, pp. 134–154.

    Google Scholar 

  96. Morley, K. C., Gallate, J. E., Hunt, G. E., Mallet, P. E., and McGregor, I. S. (2001) Increased anxiety and impaired memory in rats 3 months after administration of 3,4-methylenedioxymethamphetamine (“Ecstasy”). Eur. J. Pharmacol. 433, 91–99.

    Article  PubMed  CAS  Google Scholar 

  97. Mechan, A., Moran, P., Elliott, J. M., Young, A., Joseph, M. H., and Green, A. R. (2002) A study of the effect of a single neurotoxic dose of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) on the subsequent long-term behaviour of rats in the plus maze and open field. Psychopharmacology 159, 167–175.

    Article  PubMed  CAS  Google Scholar 

  98. Fone, K. C. F., Beckett, S. R. G., Topham, I. A., Swettenham, J., Ball, M., and Maddocks, L. (2002) Long-term changes in social interaction and reward following repeated MDMA administration to adolescent rats without accompanying serotonergic neurotoxicity. Psychopharmacology 159, 437–444.

    Article  PubMed  CAS  Google Scholar 

  99. Broening, H. W., Morford, L. L., Inman-Wood, S. L., Fukumura, M., and Vorhees, C. V. (2001) 3,4-Methylenedioxymethamphetamine (Ecstasy)-induced learning and memory impairments depend on the age of exposure during early development. J. Neurosci. 21, 3228–3235.

    PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. College of Pharmacy, University of Cincinnati, Cincinnati, OH

    Gary A. Gudelsky

  2. Department of Pharmacology, Boston University Medical School, Boston, MA

    Bryan K. Yamamoto

Authors
  1. Gary A. Gudelsky
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  2. Bryan K. Yamamoto
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Editors and Affiliations

  1. School of Pharmacy, University of Missouri-Kansas City, Kansas, USA

    John Q. Wang

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© 2003 Humana Press Inc., Totowa, NJ

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Gudelsky, G.A., Yamamoto, B.K. (2003). Neuropharmacology and Neurotoxicity of 3,4-Methylenedioxymethamphetamine. In: Wang, J.Q. (eds) Drugs of Abuse. Methods In Molecular Medicine™, vol 79. Humana Press. https://doi.org/10.1385/1-59259-358-5:55

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  • DOI: https://doi.org/10.1385/1-59259-358-5:55

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-057-1

  • Online ISBN: 978-1-59259-358-3

  • eBook Packages: Springer Protocols

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