Skip to main content
SpringerLink
Log in
Book cover

Handbook of Neurotoxicity pp 347–363Cite as

Methamphetamine and MDMA Neurotoxicity: Biochemical and Molecular Mechanisms

  • Reference work entry
  • First Online:

Abstract

Methamphetamine (METH) and its analogs, methylenedioxymethamphetamine (MDMA), are psychostimulant drugs with high abuse liability. The two drugs are also very neurotoxic. In the case of METH, the behavioral and neurotoxic effects of the drug occur because it alters dopamine terminal physiology and causes massive release of dopamine (DA) in the synaptic cleft in brain regions that receive dopaminergic projections from the midbrain. The increase of synaptic DA is compounded by the ability of METH to block DA reuptake into DA terminals. METH toxicity is not only accompanied by terminal dysfunction but also by causing dysfunction of complex networks that subserve cognitive and emotional processes. MDMA is a ring-substituted derivative of phenylisopropylamine which is structurally similar to METH. MDMA is a substrate of the serotonin transporter (SERT) via which it enters monoaminergic neurons and causes release of serotonin (5-HT) from storage vesicles. This is followed by 5-HT release into the synaptic cleft by reversal of normal SERT function. MDMA is selectively neurotoxic to serotonergic nerve terminals in rats, guinea pigs, and nonhuman primates. MDMA users consistently show reduced SERT radionuclide ligand binding across multiple brain regions. There is also evidence that MDMA users can suffer from cognitive deficits. However, the relation of DA and/or 5-HT depletion to cognitive impairments remains to be clarified in METH and MDMA users. Results from these studies are likely to impact the therapeutic approaches to the treatment of patients who suffer from METH and MDMA addiction.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   549.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   549.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Abbreviations

5-HIAA:

5-hydroxyindoleacetic acid

5-HT:

Serotonin

α-MT:

α-methyl-p-tyrosine

CNS:

Central nervous system

COMT:

Catechol-O-methyltransferase

CuZnSOD:

Copper–zinc superoxide dismutase

DA:

Dopamine

DAT:

Dopamine transporter

ER-:

Endoplasmic reticulum-

HHA:

3,4-Dihydroxyamphetamine

HHMA:

3,4-Dihydroxymethamphetamine

HMA:

4-Hydroxy-3-methoxy-amphetamine

L-DOPA:

L-3,4-Dihydroxyphenylalanine

MDA:

Methylenedioxyamphetamine

MDMA:

Methylenedioxymethamphetamine

METH:

Methamphetamine

MK-801:

Dizocilpine

MTF-1:

Metal-responsive transcription factor 1

MTs:

Metallothioneins

NET:

Norepinephrine transporter

Nrf2:

NF-E2-Related factor 2

PARP:

Poly(ADP-ribose) polymerase

ROS:

Reactive oxygen species

SERT:

Serotonin transporter

TH:

Tyrosine hydroxylase

TPH:

Tryptophan hydroxylase

VMAT2:

Vesicular monoamine transporter 2

References

  • Adori, C., Low, P., Andó, R. D., Gutknecht, L., Pap, D., Truszka, F., Takács, J., Kovács, G. G., Lesch, K. P., & Bagdy, G. (2011). Ultrastructural characterization of tryptophan hydroxylase 2-specific cortical serotonergic fibers and dorsal raphe neuronal cell bodies after MDMA treatment in rat. Psychopharmacology, 213(2–3), 377–391.

    Article  CAS  PubMed  Google Scholar 

  • Angulo, J. A., Angulo, N., & Yu, J. (2004). Antagonists of the neurokinin-1 or dopamine D1 receptors confer protection from methamphetamine on dopamine terminals of the mouse striatum. Annals of the New York Academy of Sciences, 1025, 171–180.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ares-Santos, S., Granado, N., Oliva, I., O’Shea, E., Martin, E. D., Colado, M. I., & Moratalla, R. (2012). Dopamine D(1) receptor deletion strongly reduces neurotoxic effects of methamphetamine. Neurobiology of Disease, 45(2), 810–820.

    Article  CAS  PubMed  Google Scholar 

  • Asanuma, M., Tsuji, T., Miyazaki, I., Miyoshi, K., & Ogawa, N. (2003). Methamphetamine-induced neurotoxicity in mouse brain is attenuated by ketoprofen, a non-steroidal anti-inflammatory drug. Neuroscience Letters, 352, 13–16.

    Article  CAS  PubMed  Google Scholar 

  • Asanuma, M., Miyazaki, I., Higashi, Y., Tsuji, T., & Ogawa, N. (2004). Specific gene expression and possible involvement of inflammation in methamphetamine-induced neurotoxicity. Annals of the New York Academy of Sciences, 1025, 69–75.

    Article  CAS  PubMed  Google Scholar 

  • Baucum, A. J., 2nd, Rau, K. S., Riddle, E. L., Hanson, G. R., & Fleckenstein, A. E. (2004). Methamphetamine increases dopamine transporter higher molecular weight complex formation via a dopamine- and hyperthermia-associated mechanism. Journal of Neuroscience, 24(13), 3436–3443.

    Article  CAS  PubMed  Google Scholar 

  • Baumann, M. H., & Rothman, R. B. (2009). Neural and cardiac toxicities associated with 3,4- methylenedioxymethamphetamine (MDMA). International Review of Neurobiology, 88, 257–296.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Beauvais, G., Atwell, K., Jayanthi, S., Ladenheim, B., & Cadet, J. L. (2011). Involvement of dopamine receptors in binge methamphetamine-induced activation of endoplasmic reticulum and mitochondrial stress pathways. PLoS One, 6(12), e28946.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Berridge, K. C. (2007). The debate over dopamine’s role in reward: The case for incentive salience. Psychopharmacology, 191(3), 391–431.

    Article  CAS  PubMed  Google Scholar 

  • Bhide, N. S., Lipton, J. W., Cunningham, J. I., Yamamoto, B. K., & Gudelsky, G. A. (2009). Repeated exposure to MDMA provides neuroprotection against subsequent MDMA-induced serotonin depletion in brain. Brain Research, 1286, 32–41.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Blakely, R. D., De Felice, L. J., & Hartzell, H. C. (1994). Molecular physiology of norepinephrine and serotonin transporters. Journal of Experimental Biology, 196, 263–281.

    CAS  PubMed  Google Scholar 

  • Bowyer, J. F., Davies, D. L., Schmued, L., Broening, H. W., Newport, G. D., Slikker, W., Jr., & Holson, R. R. (1994). Further studies of the role of hyperthermia in methamphetamine neurotoxicity. Journal of Pharmacology and Experimental Therapeutics, 268, 1571–1580.

    CAS  PubMed  Google Scholar 

  • Bowyer, J. F., Robinson, B., Ali, S., & Schmued, L. C. (2008). Neurotoxic-related changes in tyrosine hydroxylase, microglia, myelin, and the blood–brain barrier in the caudate-putamen from acute methamphetamine exposure. Synapse, 62(3), 193–204.

    Article  CAS  PubMed  Google Scholar 

  • Cadet, J. L. (1988). A unifying theory of movement and madness: Involvement of free radicals in disorders of the isodendritic core of the brainstem. Medical Hypotheses, 27(1), 59–63.

    Article  CAS  PubMed  Google Scholar 

  • Cadet, J. L., & Brannock, C. (1998). Free radicals and the pathobiology of brain dopamine systems. Neurochemistry International, 32(2), 117–131.

    Article  CAS  PubMed  Google Scholar 

  • Cadet, J. L., Ali, S., & Epstein, C. (1994a). Involvement of oxygen-based radicals in methamphetamine-induced neurotoxicity: Evidence from the use of CuZnSOD transgenic mice. Annals of the New York Academy of Sciences, 738, 388–391.

    Article  CAS  PubMed  Google Scholar 

  • Cadet, J. L., Sheng, P., Ali, S., Rothman, R., Carlson, E., & Epstein, C. (1994b). Attenuation of methamphetamine-induced neurotoxicity in copper/zinc superoxide dismutase transgenic mice. Journal of Neurochemistry, 62, 380–383.

    Article  CAS  PubMed  Google Scholar 

  • Cadet, J. L., Ladenheim, B., Hirata, H., Rothman, R. B., Ali, S., Carlson, E., Epstein, C., & Moran, T. H. (1995). Superoxide radicals mediate the biochemical effects of methylenedioxymethamphetamine (MDMA): Evidence from using CuZn-superoxide dismutase transgenic mice. Synapse, 21, 169–176.

    Article  CAS  PubMed  Google Scholar 

  • Cadet, J. L., McCoy, M. T., & Ladenheim, B. (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.

    Article  CAS  PubMed  Google Scholar 

  • Cadet, J. L., Krasnova, I. N., Ladenheim, B., Cai, N. S., McCoy, M. T., & Atianjoh, F. E. (2009). Methamphetamine preconditioning: Differential protective effects on monoaminergic systems in the rat brain. Neurotoxicity Research, 15(3), 252–259.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cadet, J. L., Brannock, C., Ladenheim, B., McCoy, M. T., Beauvais, G., Hodges, A. B., Lehrmann, E., Wood, W. H., 3rd, Becker, K. G., & Krasnova, I. N. (2011). Methamphetamine preconditioning causes differential changes in striatal transcriptional responses to large doses of the drug. Dose–response, 9(2), 165–181.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Callahan, B. T., Cord, B. J., & 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(2), 113–121.

    Article  CAS  PubMed  Google Scholar 

  • Chipana, C., Torres, I., Camarasa, J., Pubill, D., & Escubedo, E. (2008). Memantine protects against amphetamine derivatives-induced neurotoxic damage in rodents. Neuropharmacology, 54(8), 1254–1263.

    Article  CAS  PubMed  Google Scholar 

  • Commins, D. L., Vosmer, G., Virus, R. M., Woolverton, W. L., Schuster, C. R., & Seiden, L. S. (1987). Biochemical and histological evidence that methylenedioxymethylamphetamine (MDMA) is toxic to neurons in the rat brain. Journal of Pharmacology and Experimental Therapeutics, 241, 338–345.

    CAS  PubMed  Google Scholar 

  • Danaceau, J. P., Deering, C. E., Day, J. E., Smeal, S. J., Johnson-Davis, K. L., Fleckenstein, A. E., & Wilkins, D. G. (2007). Persistence of tolerance to methamphetamine-induced monoamine deficits. European Journal of Pharmacology, 559(1), 46–54.

    Article  CAS  PubMed  Google Scholar 

  • Darke, S., Kaye, S., McKetin, R., & Duflou, J. (2008). Major physical and psychological harms of methamphetamine use. Drug and Alcohol Review, 27(3), 253–262.

    Article  PubMed  Google Scholar 

  • De Souza, E. B., Battaglia, G., & Insel, T. R. (1990). Neurotoxic effect of MDMA on brain serotonin neurons: Evidence from neurochemical and radioligand binding studies. Annals of the New York Academy of Sciences, 600, 682–697.

    Article  PubMed  Google Scholar 

  • Deng, X., & Cadet, J. L. (2000). Methamphetamine-induced apoptosis is attenuated in the striata of copper-zinc superoxide dismutase transgenic mice. Brain Research. Molecular Brain Research, 83, 121–124.

    Article  CAS  PubMed  Google Scholar 

  • Deng, X., Ladenheim, B., Tsao, L. I., & Cadet, J. L. (1999). Null mutation of c-fos causes exacerbation of methamphetamine-induced neurotoxicity. Journal of Neuroscience, 19(22), 10107–10115.

    CAS  PubMed  Google Scholar 

  • Deng, X., Wang, Y., Chou, J., & Cadet, J. L. (2001). Methamphetamine causes widespread apoptosis in the mouse brain: Evidence from using an improved TUNEL histochemical method. Brain Research. Molecular Brain Research, 93, 64–69.

    Article  CAS  PubMed  Google Scholar 

  • Deng, X., Ladenheim, B., Jayanthi, S., & Cadet, J. L. (2007). Methamphetamine administration causes death of dopaminergic neurons in the mouse olfactory bulb. Biological Psychiatry, 61(11), 1235–1243.

    Article  CAS  PubMed  Google Scholar 

  • El Ayadi, A., & Zigmond, M. J. (2011). Low concentrations of methamphetamine can protect dopaminergic cells against a larger oxidative stress injury: Mechanistic study. PLoS One, 6(10), e24722.

    Article  PubMed Central  PubMed  Google Scholar 

  • Erritzoe, D., Frokjaer, V. G., Holst, K. K., Christoffersen, M., Johansen, S. S., Svarer, C., Madsen, J., Rasmussen, P. M., Ramsøy, T., Jernigan, T. L., & Knudsen, G. M. (2011). In vivo imaging of cerebral serotonin transporter and serotonin2A receptor binding in 3,4-methylenedioxymethamphetamine (MDMA or “ecstasy”) and hallucinogen users. Archives of General Psychiatry, 68(6), 562–576.

    Article  PubMed  Google Scholar 

  • Eyerman, D. J., & Yamamoto, B. K. (2005). Lobeline attenuates methamphetamine-induced changes in vesicular monoamine transporter 2 immunoreactivity and monoamine depletions in the striatum. Journal of Pharmacology and Experimental Therapeutics, 312, 160–169.

    Article  CAS  PubMed  Google Scholar 

  • Fumagalli, F., Gainetdinov, R. R., Valenzano, K. J., & Caron, M. G. (1998). Role of dopamine transporter in methamphetamine-induced neurotoxicity: Evidence from mice lacking the transporter. Journal of Neuroscience, 18, 4861–4869.

    CAS  PubMed  Google Scholar 

  • Gerra, G., Zaimovic, A., Ferri, M., Zambelli, U., Timpano, M., Neri, E., Marzocchi, G. F., Delsignore, R., & Brambilla, F. (2000). Long-lasting effects of (+/−)3,4- methylenedioxymethamphetamine (ecstasy) on serotonin system function in humans. Biological Psychiatry, 47(2), 127–136.

    Article  CAS  PubMed  Google Scholar 

  • Gonzalez, R., Rippeth, J. D., Carey, C. L., Heaton, R. K., Moore, D. J., Schweinsburg, B. C., Cherner, M., & Grant, I. (2004). Neurocognitive performance of methamphetamine users discordant for history of marijuana exposure. Drug and Alcohol Dependence, 76(2), 181–190.

    Article  CAS  PubMed  Google Scholar 

  • Graham, D. L., Noailles, P. A., & Cadet, J. L. (2008). Differential neurochemical consequences of an escalating dose-binge regimen followed by single-day multiple-dose methamphetamine challenges. Journal of Neurochemistry, 105(5), 1873–1885.

    Article  CAS  PubMed  Google Scholar 

  • Granado, N., Ares-Santos, S., Oliva, I., O’Shea, E., Martin, E. D., Colado, M. I., & Moratalla, R. (2011a). Dopamine D2-receptor knockout mice are protected against dopaminergic neurotoxicity induced by methamphetamine or MDMA. Neurobiology of Disease, 42(3), 391–403.

    Article  CAS  PubMed  Google Scholar 

  • Granado, N., Lastres-Becker, I., Ares-Santos, S., Oliva, I., Martin, E., Cuadrado, A., & Moratalla, R. (2011b). Nrf2 Deficiency potentiates methamphetamine-induced dopaminergic axonal damage and gliosis in the striatum. Glia, 59, 1.

    Article  Google Scholar 

  • Green, A. R., Cross, A. J., & Goodwin, G. M. (1995). Review of the pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA or ‘Ecstasy’). Psychopharmacology, 119, 247–260.

    Article  CAS  PubMed  Google Scholar 

  • Green, A. R., Mechan, A. O., Elliott, J. M., O’Shea, E., & Colado, M. I. (2003). The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”). Pharmacological Reviews, 55(3), 463–508.

    Article  CAS  PubMed  Google Scholar 

  • Hadlock, G. C., Baucum, A. J., II, King, J. L., Horner, K. A., Cook, G. A., Gibb, J. W., Wilkins, D. G., Hanson, G. R., & Fleckenstein, A. E. (2009). Mechanisms underlying methamphetamine-induced dopamine transporter complex formation. Journal of Pharmacology and Experimental Therapeutics, 329(1), 169–174.850–1863.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hodges, A. B., Ladenheim, B., McCoy, M. T., Beauvais, G., Cai, N., Krasnova, I. N., & Cadet, J. L. (2011). Long-term protective effects of methamphetamine preconditioning against single-day methamphetamine toxic challenges. Current Neuropharmacology, 9, 35–39.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Homer, B. D., Solomon, T. M., Moeller, R. W., Mascia, A., DeRaleau, L., & Halkitis, P. N. (2008). Methamphetamine abuse and impairment of social functioning: A review of the underlying neurophysiological causes and behavioral implications. Psychological Bulletin, 134(2), 301–310.

    Article  PubMed  Google Scholar 

  • Jayanthi, S., Ladenheim, B., & Cadet, J. L. (1998). Methamphetamine-induced changes in antioxidant enzymes and lipid peroxidation in copper/zinc-superoxide dismutase transgenic mice. Annals of the New York Academy of Sciences, 844, 92–102.

    Article  CAS  PubMed  Google Scholar 

  • Jayanthi, S., Deng, X., Ladenheim, B., McCoy, M. T., Cluster, A., Cai, N. S., & Cadet, J. L. (2005). Calcineurin/NFAT-induced up-regulation of the Fas ligand/Fas death pathway is involved in methamphetamine-induced neuronal apoptosis. Proceeding of the National Academy of Sciences USA, 102, 868–873.

    Article  CAS  Google Scholar 

  • Jayanthi, S., McCoy, M. T., Beauvais, G., Ladenheim, B., Gilmore, K., Wood, W., III, Becker, K., & Cadet, J. L. (2009). Methamphetamine induces dopamine D1 receptor-dependent endoplasmic reticulum stress-related molecular events in the rat striatum. PLoS One, 4(6), e6092.

    Article  PubMed Central  PubMed  Google Scholar 

  • Kish, S. J., Lerch, J., Furukawa, Y., Tong, J., McCluskey, T., Wilkins, D., Houle, S., Meyer, J., Mundo, E., Wilson, A. A., Rusjan, P. M., Saint-Cyr, J. A., Guttman, M., Collins, D. L., Shapiro, C., Warsh, J. J., & Boileau, I. (2010). Decreased cerebral cortical serotonin transporter binding in ecstasy users: A positron emission tomography/[11C]DASB and structural brain imaging study. Brain, 133, 1779–1797.

    Article  PubMed Central  PubMed  Google Scholar 

  • Kivell, B., Day, D., Bosch, P., Schenk, S., & Miller, J. (2010). MDMA causes a redistribution of serotonin transporter from the cell surface to the intracellular compartment by a mechanism independent of phospho-p38-mitogen activated protein kinase activation. Neuroscience, 168(1), 82–95.

    Article  CAS  PubMed  Google Scholar 

  • Krasnova, I. N., & Cadet, J. L. (2009). Methamphetamine toxicity and messengers of death. Brain Research Reviews, 60(2), 379–407.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Krasnova, I. N., Justinova, Z., Ladenheim, B., Jayanthi, S., McCoy, M. T., Barnes, C., Warner, J. E., Goldberg, S. R., & Cadet, J. L. (2010). Methamphetamine self-administration is associated with persistent biochemical alterations in striatal and cortical dopaminergic terminals in the rat. PLoS One, 5(1), e8790.

    Article  PubMed Central  PubMed  Google Scholar 

  • Krasnova, I. N., Ladenheim, B., Hodges, A. B., Volkow, N. D., & Cadet, J. L. (2011). Chronic methamphetamine administration causes differential regulation of transcription factors in the rat midbrain. PLoS One, 6(4), E19179.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kuhn, D. M., Francescutti-Verbeem, D. M., & Thomas, D. M. (2008). Dopamine disposition in the presynaptic process regulates the severity of methamphetamine-induced neurotoxicity. Annals of the New York Academy of Sciences, 1139, 118–126.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ladenheim, B., Krasnova, I. N., Deng, X., Oyler, J. M., Polettini, A., Moran, T. H., Huestis, M. A., & Cadet, J. L. (2000). Methamphetamine-induced neurotoxicity is attenuated in transgenic mice with a null mutation for interleukin-6. Molecular Pharmacology, 58, 1247–1256.

    CAS  PubMed  Google Scholar 

  • Le Moal, M., & Koob, G. F. (2007). Drug addiction: Pathways to the disease and pathophysiological perspectives. European Neuropsychopharmacology, 6–7, 377–393.

    Article  Google Scholar 

  • Li, Y., & Trush, M. A. (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.

    Article  CAS  PubMed  Google Scholar 

  • Li, I. H., Huang, W. S., Shiue, C. Y., Huang, Y. Y., Liu, R. S., Chyueh, S. C., Hu, S. H., Liao, M. H., Shen, L. H., Liu, J. C., & Ma, K. H. (2010). Study on the neuroprotective effect of fluoxetine against MDMA-induced neurotoxicity on the serotonin transporter in rat brain using micro-PET. NeuroImage, 49(2), 1259–1270.

    Article  PubMed  Google Scholar 

  • Lyles, J., & Cadet, J. L. (2003). Methylenedioxymethamphetamine (MDMA, ecstasy) neurotoxicity: Cellular and molecular mechanisms. Brain Research. Brain Research Reviews, 42(2), 155–168.

    Article  CAS  PubMed  Google Scholar 

  • McCann, U. D., & Ricaurte, G. A. (2004). Amphetamine neurotoxicity: Accomplishments and remaining challenges. Neuroscience and Biobehavioral Reviews, 27(8), 821–826.

    Article  CAS  PubMed  Google Scholar 

  • McCann, U. D., Wong, D. F., Yokoi, F., Villemagne, V., Dannals, R. F., & Ricaurte, G. A. (1998). Reduced striatal dopamine transporter density in abstinent methamphetamine and methcathinone users: Evidence from positron emission tomography studies with [11C]WIN-35,428. Journal of Neuroscience, 18(20), 8417–8422.

    CAS  PubMed  Google Scholar 

  • McFadden, L. M., Hadlock, G. C., Allen, S. C., Vieira-Brock, P. L., Stout, K. A., Ellis, J. D., Hoonakker, A. J., Andrenyak, D. M., Nielsen, S. M., Wilkins, D. G., Hanson, G. R., & Fleckenstein, A. E. (2012). Methamphetamine self-administration causes persistent striatal dopaminergic alterations and mitigates the deficits caused by a subsequent methamphetamine exposure. Journal of Pharmacology and Experimental Therapeutics, 340(2), 295–303.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Miyazaki, I., Asanuma, M., Kikkawa, Y., Takeshima, M., Murakami, S., Miyoshi, K., Sogawa, N., & Kita, T. (2010). Astrocyte-derived metallothionein protects dopaminergic neurons from dopamine quinone toxicity. Glia, 59(3), 435–451.

    Article  PubMed  Google Scholar 

  • O’Callaghan, J. P., & Miller, D. B. (1994). Neurotoxicity profiles of substituted amphetamines in the C57BL/6 J mouse. Journal of Pharmacology and Experimental Therapeutics, 270, 741–751.

    PubMed  Google Scholar 

  • Parrott, A. C. (2006). MDMA in humans: Factors which affect the neuropsychobiological profiles of recreational ecstasy users, the integrative role of bio-energetic stress. Journal of Psychopharmacology, 20, 147–163.

    Article  CAS  PubMed  Google Scholar 

  • Pubill, D., Verdaguer, E., Sureda, F. X., Camins, A., Pallas, M., Camarasa, J., & Escubedo, E. (2002). Carnosine prevents methamphetamine-induced gliosis but not dopamine terminal loss in rats. European Journal of Pharmacology, 448, 165–168.

    Article  CAS  PubMed  Google Scholar 

  • Raineri, M., Peskin, V., Goitia, B., Taravini, I. R., Giorgeri, S., Urbano, F. J., & Bisagno, V. (2011). Attenuated methamphetamine induced neurotoxicity by modafinil administration in mice. Synapse, 65(10), 1087–1098.

    Article  CAS  PubMed  Google Scholar 

  • Raivich, G. (2005). Like cops on the beat: The active role of resting microglia. Trends in Neurosciences, 11, 571–573.

    Article  Google Scholar 

  • Reneman, L., Endert, E., de Bruin, K., Lavalaye, J., Feenstra, M. G., de Wolff, F. A., & Booij, J. (2002). The acute and chronic effects of MDMA (“ecstasy”) on cortical 5-HT2A receptors in rat and human brain. Neuropsychopharmacology, 26, 387–396.

    Article  CAS  PubMed  Google Scholar 

  • Reneman, L., de Win, M. M., van den Brink, W., Booij, J., & den Heeten, G. J. (2006). Neuroimaging findings with MDMA/ecstasy: Technical aspects, conceptual issues and future prospects. Journal of Psychopharmacology, 20, 164–175.

    Article  CAS  PubMed  Google Scholar 

  • Ricaurte, G. A., Guillery, R. W., Seiden, L. S., Schuster, C. R., & Moore, R. Y. (1982). Dopamine nerve terminal degeneration produced by high doses of methylamphetamine in the rat brain. Brain Research, 235(1), 93–103.

    Article  CAS  PubMed  Google Scholar 

  • Ricaurte, G. A., Yuan, J., & McCann, U. D. (2000). (+/−)3,4-Methylenedioxymethamphetamine (‘Ecstasy’)-induced serotonin neurotoxicity: Studies in animals. Neuropsychobiology, 42(1), 5–10.

    Article  CAS  PubMed  Google Scholar 

  • Sandoval, V., Riddle, E. L., Hanson, G. R., & Fleckenstein, A. E. (2003). Methylphenidate alters vesicular monoamine transport and prevents methamphetamine-induced dopaminergic deficits. Journal of Pharmacology and Experimental Therapeutics, 304(3), 1181–1187.

    CAS  PubMed  Google Scholar 

  • Sekine, Y., Minabe, Y., Ouchi, Y., Takei, N., Iyo, M., Nakamura, K., Suzuki, K., Tsukada, H., Okada, H., Yoshikawa, E., Futatsubashi, M., & Mori, N. (2003). Association of dopamine transporter loss in the orbitofrontal and dorsolateral prefrontal cortices with methamphetamine-related psychiatric symptoms. The American Journal of Psychiatry, 160, 1699–1701.

    Article  PubMed  Google Scholar 

  • Sekine, Y., Ouchi, Y., Sugihara, G., Takei, N., Yoshikawa, E., Nakamura, K., Iwata, Y., Tsuchiya, K. J., Suda, S., Suzuki, K., Kawai, M., Takebayashi, K., Yamamoto, S., Matsuzaki, H., Ueki, T., Mori, N., Gold, M. S., & Cadet, J. L. (2008). Methamphetamine causes microglial activation in the brains of human abusers. Journal of Neuroscience, 28, 5756–5761.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Shioda, K., Nisijima, K., Yoshino, T., Kuboshima, K., Iwamura, T., Yui, K., & Kato, S. (2008). Risperidone attenuates and reverses hyperthermia induced by 3,4- methylenedioxymethamphetamine (MDMA) in rats. Neurotoxicology, 29(6), 1030–1036.

    Article  CAS  PubMed  Google Scholar 

  • Sonsalla, P. K., Gibb, J. W., & Hanson, G. R. (1986). Roles of D1 and D2 dopamine receptor subtypes in mediating the methamphetamine-induced changes in monoamine systems. Journal of Pharmacology and Experimental Therapeutics, 238, 932–937.

    CAS  PubMed  Google Scholar 

  • Sulzer, D., & Rayport, S. (1990). Amphetamine and other psychostimulants reduce pH gradients in midbrain dopaminergic neurons and chromaffin granules: A mechanism of action. Neuron, 5(6), 797–808.

    Article  CAS  PubMed  Google Scholar 

  • Sulzer, D., Sonders, M. S., Poulsen, N. W., & Galli, A. (2005). Mechanisms of neurotransmitter release by amphetamines: A review. Progress in Neurobiology, 75(6), 406–433.

    Article  CAS  PubMed  Google Scholar 

  • Thomas, D. M., & Kuhn, D. M. (2005a). Attenuated microglial activation mediates tolerance to the neurotoxic effects of methamphetamine. Journal of Neurochemistry, 92, 790–797.

    Article  CAS  PubMed  Google Scholar 

  • Thomas, D. M., & Kuhn, D. M. (2005b). MK-801 and dextromethorphan block microglial activation and protect against methamphetamine-induced neurotoxicity. Brain Research, 1050, 190–198.

    Article  CAS  PubMed  Google Scholar 

  • Thomas, D. M., Dowgiert, J., Geddes, T. J., Francescutti-Verbeem, D., Liu, X., & Kuhn, D. M. (2004a). Microglial activation is a pharmacologically specific marker for the neurotoxic amphetamines. Neuroscience Letters, 367, 349–354.

    Article  CAS  PubMed  Google Scholar 

  • Thomas, D. M., Walker, P. D., Benjamins, J. A., Geddes, T. J., & Kuhn, D. M. (2004b). Methamphetamine neurotoxicity in dopamine nerve endings of the striatum is associated with microglial activation. Journal of Pharmacology and Experimental Therapeutics, 311, 1–7.

    Article  CAS  PubMed  Google Scholar 

  • Thomas, D. M., Francescutti-Verbeem, D. M., & Kuhn, D. M. (2008). The newly synthesized pool of dopamine determines the severity of methamphetamine-induced neurotoxicity. Journal of Neurochemistry, 105(3), 605–616.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Verdejo-García, A., Bechara, A., Recknor, E. C., & Pérez-García, M. (2006). Executive dysfunction in substance dependent individuals during drug use and abstinence: An examination of the behavioral, cognitive and emotional correlates of addiction. Journal of International Neuropsychological Society, 12(3), 405–415.

    Article  Google Scholar 

  • Volkow, N. D., Chang, L., Wang, G. J., Fowler, J. S., Franceschi, D., Sedler, M., Gatley, S. J., Miller, E., Hitzemann, R., Ding, Y. S., & Logan, J. (2001a). Loss of dopamine transporters in methamphetamine abusers recovers with protracted abstinence. Journal of Neuroscience, 21, 9414–9418.

    CAS  PubMed  Google Scholar 

  • Volkow, N. D., Chang, L., Wang, G. J., Fowler, J. S., Franceschi, D., Sedler, M. J., Gatley, S. J., Hitzemann, R., Ding, Y. S., Wong, C., & Logan, J. (2001b). Higher cortical and lower subcortical metabolism in detoxified methamphetamine abusers. The American Journal of Psychiatry, 58, 383–389.

    Article  Google Scholar 

  • Volkow, N. D., Chang, L., Wang, G. J., Fowler, J. S., Leonido-Yee, M., Franceschi, D., Sedler, M. J., Gatley, S. J., Hitzemann, R., Ding, Y. S., Logan, J., Wong, C., & Miller, E. N. (2001c). Association of dopamine transporter reduction with psychomotor impairment in methamphetamine abusers. The American Journal of Psychiatry, 158, 377–382.

    Article  CAS  PubMed  Google Scholar 

  • Wang, G. J., Volkow, N. D., Chang, L., Miller, E., Sedler, M., Hitzemann, R., Zhu, W., Logan, J., Ma, Y., & Fowler, J. S. (2004). Partial recovery of brain metabolism in methamphetamine abusers after protracted abstinence. The American Journal of Psychiatry, 161(2), 242–248.

    Article  PubMed  Google Scholar 

  • Xu, W., Zhu, J. P., & Angulo, J. A. (2005). Induction of striatal pre- and postsynaptic damage by methamphetamine requires the dopamine receptors. Synapse, 58, 110–121.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang, L., Kitaichi, K., Fujimoto, Y., Nakayama, H., Shimizu, E., Iyo, M., & Hashimoto, K. (2006). Protective effects of minocycline on behavioral changes and neurotoxicity in mice after administration of methamphetamine. Progress in Neuropsychopharmacology and Biological Psychiatry, 30, 1381–1393.

    Article  CAS  Google Scholar 

  • Zolkowska, D., Jain, R., Rothman, R. B., Partilla, J. S., Roth, B. L., Setola, V., Prisinzano, T. E., & Baumann, M. H. (2009). Evidence for the involvement of dopamine transporters in behavioral stimulant effects of modafinil. Journal of Pharmacology and Experimental Therapeutics, 329, 738–746.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Instituto de Investigaciones Farmacológicas (ININFA-UBA-CONICET), Junín 956, piso 5 C1113, Buenos Aires, Argentina

    Verónica Bisagno

  2. NIDA Intramural Program, Molecular Neuropsychiatry Research Branch, NIDA/NIH/DHHS, 251 Bayview Boulevard, Baltimore, MD, 21224, USA

    Jean Lud Cadet

Authors
  1. Verónica Bisagno
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jean Lud Cadet
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jean Lud Cadet .

Editor information

Editors and Affiliations

  1. Department of Biomedical Sciences, East Tennessee State University, Johnson City, Tennessee, USA

    Richard M. Kostrzewa

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this entry

Cite this entry

Bisagno, V., Cadet, J.L. (2014). Methamphetamine and MDMA Neurotoxicity: Biochemical and Molecular Mechanisms. In: Kostrzewa, R. (eds) Handbook of Neurotoxicity. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5836-4_80

Download citation

Publish with us

Policies and ethics

Search

Navigation