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Methamphetamine and MDMA Neurotoxicity: Biochemical and Molecular Mechanisms

  • Living reference work entry
  • First Online:
Handbook of Neurotoxicity

Abstract

Methamphetamine (METH) and methylenedioxymethamphetamine (MDMA) are psychostimulant drugs that are widely abused. The two drugs can also cause neurotoxic damage and neurodegeneration in several regions of the brains of humans, nonhuman primates, and rodents. METH-induced behavioral and neurotoxic abnormalities occur consequent to alterations of dopamine terminal physiology, which leads to massive release of dopamine (DA) in the synaptic clefts of several brain regions. Increased DA levels in synaptic clefts are further enhanced by METH-induced blockade of DA re-uptake into DA terminals through the DA transporter (DAT). METH toxicity is not only accompanied by terminal dysfunctions/degeneration but also by impairments in complex networks that subserve cognitive and emotional processes. MDMA, a ring-substituted derivative of phenyl-isopropylamine, is structurally similar to METH. MDMA is a substrate of the serotonin transporter (SERT) through which it enters monoaminergic terminals where it triggers release of serotonin (5-HT) from storage vesicles into synaptic clefts of brain regions that receive serotoninergic terminals from the ventral and dorsal midbrain raphe nuclei. In addition, MDMA has been shown to cause selectively neurotoxic damage to serotonergic nerve terminals in rats, guinea pigs, and nonhuman primates even though toxic damage to the human brain has been debatable. There is also evidence that some MDMA users exhibit cognitive deficits. Nevertheless, there is, at present, no firm evidence that links drug-induced DA and/or 5-HT depletion to cognitive impairments. More studies are necessary to clarify the importance of these changes in the development of beneficial therapeutics to the treatment of patients who suffer from METH and MDMA use disorders.

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Abbreviations

ADHD:

Attention Deficit Hyperactivity Disorder

ATG:

Autophagy-related genes

DA:

Dopamine

DAT:

Dopamine transporter

ER:

Endoplasmic Reticulum

5-HIAA:

5-hydroxyindoleacetic acid

α-MT:

α-methyl-p-tyrosine

COMT:

catechol-O-methyltransferase

CNS:

Central Nervous System

CuZnSOD:

copper-zinc superoxide dismutase

HHA:

3,4-dihydroxyamphetamine

HHMA:

3,4-dihydroxymethamphetamine

HMA:

4-hydroxy-3-methoxy-amphetamine

5-HT:

serotonin

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

SERT:

serotonin transporter

ROS:

Reactive Oxygen species

TPH:

tryptophan hydroxylase

TH:

tyrosine hydroxylase

ULK1:

autophagy activating kinase

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. Annual New York Academy of Sciences, 1025, 171–180.

    Article  CAS  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. Annual New York Academy of Sciences, 1025, 69–75.

    Article  CAS  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  PubMed Central  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 

  • Beaulieu, J. M., Espinoza, S., & Gainetdinov, R. R. (2015). Dopamine receptors – IUPHAR review 13. British Journal of Pharmacology, 172(1), 1–23.

    Article  CAS  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  PubMed Central  Google Scholar 

  • Berridge, K. C., & Robinson, T. E. (2016). Liking, wanting, and the incentive-sensitization theory of addiction. The American Psychologist, 71(8), 670–679.

    Article  PubMed  PubMed Central  Google Scholar 

  • Bershad, A. K., Miller, M. A., Baggott, M. J., & de Wit, H. (2016). The effects of MDMA on socio-emotional processing: Does MDMA differ from other stimulants? Journal of Psychopharmacology, 30, 1248–1258.

    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  PubMed Central  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.

    Article  CAS  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  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. (1988a). Free radical mechanisms in the central nervous system: An overview. International Journal of Neuroscience, 40(1–2), 13–18.

    Article  CAS  Google Scholar 

  • Cadet, J. L. (1988b). 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., Ali, S., & Epstein, C. (1994a). Involvement of oxygen-based radicals in methamphetamine-induced neurotoxicity: Evidence from the use of CuZnSOD transgenic mice. Annual New York Academy of Sciences, 738, 388–391.

    Article  CAS  Google Scholar 

  • Cadet, J. L., & Bisagno, V. (2016). Neuropsychological consequences of chronic drug use: Relevance to treatment approaches. Frontiers in Psychiatry, 6, 189.

    Article  PubMed  PubMed Central  Google Scholar 

  • Cadet, J. L., Bisagno, V., & Milroy, C. M. (2014). Neuropathology of substance use disorders. Acta Neuropathologica, 127(1), 91–107.

    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., 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.

    Article  CAS  PubMed  Google Scholar 

  • Cadet, J. L., Jayanthi, S., & Deng, X. (2003). Speed kills: Cellular and molecular bases of methamphetamine-induced nerve terminal degeneration and neuronal apoptosis. FASEB Journal, 17(13), 1775–1788.

    Article  CAS  PubMed  Google Scholar 

  • Cadet, J. L., Jayanthi, S., & Deng, X. (2005). Methamphetamine-induced neuronal apoptosis involves the activation of multiple death pathways. Review. Neurotoxicity Research, 8(3–4), 199–206.

    Article  CAS  PubMed  Google Scholar 

  • Cadet, J. L., Jayanthi, S., McCoy, M. T., Vawter, M., & Ladenheim, B. (2001). Temporal profiling of methamphetamine-induced changes in gene expression in the mouse brain: Evidence from cDNA array. Synapse, 41(1), 40–48.

    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  PubMed Central  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 

  • 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 

  • Callaghan, R. C., Cunningham, J. K., Sykes, J., & Kish, S. J. (2012). Increased risk of Parkinson’s disease in individuals hospitalized with conditions related to the use of methamphetamine or other amphetamine-type drugs. Drug and Alcohol Dependence, 20(1–3), 35–40.

    Article  Google Scholar 

  • Castells, X., Blanco-Silvente, L., & Cunill, R. (2018). Amphetamines for attention deficit hyperactivity disorder (ADHD) in adults. Cochrane Database Systematic Reviews, 8(8), CD007813.

    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 

  • Chomchai, C., & Chomchai, S. (2015). Global patterns of methamphetamine use. Current Opinion in Psychiatry, 28(4), 269–274.

    Article  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  Google Scholar 

  • Cubells, J. F., Rayport, S., Rajendran, G., & Sulzer, D. (1994). Methamphetamine neurotoxicity involves vacuolation of endocytic organelles and dopamine-dependent intracellular oxidative stress. Journal of Neuroscience, 14(4), 2260–2271.

    Article  CAS  PubMed  Google Scholar 

  • Curry, D. W., Young, M. B., Tran, A. N., Daoud, G. E., & Howell, L. L. (2018). Separating the agony from ecstasy: R(−)-3, 4-methylenedioxymethamphetamine has prosocial and therapeutic-like effects without signs of neurotoxicity in mice. Neuropharmacology, 128, 196–206.

    Article  CAS  PubMed  Google Scholar 

  • Curtin, K., Fleckenstein, A. E., Robison, R. J., Crookston, M. J., Smith, K. R., & Hanson, G. R. (2015). Methamphetamine/amphetamine abuse and risk of Parkinson’s disease in Utah: A population-based assessment. Drug and Alcohol Dependence, 146, 30–38.

    Article  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. Annual New York Academy of Sciences, 600, 682–697.

    Article  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.

    Article  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 

  • Dolder, P. C., Müller, F., Schmid, Y., Borgwardt, S. J., & Liechti, M. E. (2018). Direct comparison of the acute subjective, emotional, autonomic, and endocrine effects of MDMA, methylphenidate, and modafinil in healthy subjects. Psychopharmacology (Berlin), 235(2), 467–479.

    Article  CAS  Google Scholar 

  • Dunlap, L. E., Andrews, A. M., & Olson, D. E. (2018). Dark classics in chemical neuroscience: 3,4-methylenedioxymethamphetamine. ACS Chemical Neuroscience, 9(10), 2408–2427.

    Article  CAS  PubMed  Google Scholar 

  • Dwoskin, L. P., & Crooks, P. A. (2002). A novel mechanism of action and potential use for lobeline as a treatment for psychostimulant abuse. Biochemical Pharmacology, 63(2), 89–98.

    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  PubMed Central  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  Google Scholar 

  • Frau, L., Simola, N., Plumitallo, A., & Morelli, M. (2013). Microglial and astroglial activation by 3,4- methylenedioxymethamphetamine (MDMA) in mice depends on S(+) enantiomer and is associated with an increase in body temperature and motility. Journal of Neurochemistry, 124, 69–78.

    Article  CAS  PubMed  Google Scholar 

  • Fumagalli, F., Gainetdinov, R. R., Wang, Y. M., Valenzano, K. J., Miller, G. W., & Caron, M. G. (1999). Increased methamphetamine neurotoxicity in heterozygous vesicular monoamine transporter 2 knock-out mice. Journal of Neuroscience, 19(7), 2424–2431.

    Article  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 

  • Gonçalves, J., Leitão, R. A., Higuera-Matas, A., Assis, M. A., Coria, S. M., Fontes-Ribeiro, C., Ambrosio, E., & Silva, A. P. (2017). Extended-access methamphetamine self-administration elicits neuroinflammatory response along with blood-brain barrier breakdown. Brain Behavior and Immunity, 62, 306–317.

    Article  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 

  • Górska, A. M., Kamińska, K., Wawrzczak-Bargieła, A., Costa, G., Morelli, M., Przewłocki, R., Kreiner, G., & Gołembiowska, K. (2018). Neurochemical and neurotoxic effects of MDMA (ecstasy) and caffeine after chronic combined administration in mice. Neurotoxicity Research, 33(3), 532–548.

    Article  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., 2nd, 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  Google Scholar 

  • Harro, J. (2015). Neuropsychiatric adverse effects of amphetamine and methamphetamine. International Review of Neurobiology, 120, 179–204.

    Article  CAS  PubMed  Google Scholar 

  • Herndon, J. M., Cholanians, A. B., Lau, S. S., & Monks, T. J. (2014). Glial cell response to 3,4-(+/−)-methylenedioxymethamphetamine and its metabolites. Toxicological Sciences, 138(1), 130–138.

    Article  CAS  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  PubMed Central  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., Deng, X., Noailles, P. A., Ladenheim, B., & Cadet, J. L. (2004). Methamphetamine induces neuronal apoptosis via cross-talks between endoplasmic reticulum and mitochondria-dependent death cascades. FASEB Journal, 18(2), 238–251.

    Article  CAS  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. Annual New York Academy of Sciences, 844, 92–102.

    Article  CAS  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. Proceedings of the National Academy of Sciences of the United States of America, 102, 868–873.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jayanthi, S., McCoy, M. T., Beauvais, G., Ladenheim, B., Gilmore, K., Wood, W., 3rd, 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  PubMed Central  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  PubMed Central  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 

  • Kousik, S. M., Carvey, P. M., & Napier, T. C. (2014). Methamphetamine self-administration results in persistent dopaminergic pathology: Implications for Parkinson’s disease risk and reward-seeking. European Journal of Neuroscience, 40, 2707–2714.

    Article  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  PubMed Central  Google Scholar 

  • Krasnova, I. N., Justinova, Z., & Cadet, J. L. (2016). Methamphetamine addiction: Involvement of CREB and neuroinflammatory signaling pathways. Psychopharmacology (Berlin), 233(10), 1945–1962.

    Article  CAS  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  PubMed Central  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  PubMed Central  Google Scholar 

  • Krasnova, I. N., Chiflikyan, M., Justinova, Z., McCoy, M. T., Ladenheim, B., Jayanthi, S., Quintero, C., Brannock, C., Barnes, C., Adair, J. E., Lehrmann, E., Kobeissy, F. H., Gold, M. S., Becker, K. G., Goldberg, S. R., & Cadet, J. L. (2013). CREB phosphorylation regulates striatal transcriptional responses in the self-administration model of methamphetamine addiction in the rat. Neurobiology of Disease, 58, 132–143.

    Google Scholar 

  • Krediet, E., Bostoen, T., Breeksema, J., van Schagen, A., Passie, T., & Vermetten, E. (2020). Reviewing the potential of psychedelics for the treatment of PTSD. International Journal of Neuropsychopharmacology, 23(6), 385–400.

    Article  CAS  PubMed Central  Google Scholar 

  • Kreisl, W. C., Kim, M. J., Coughlin, J. M., Henter, I. D., Owen, D. R., & Innis, R. B. (2020). PET imaging of neuroinflammation in neurological disorders. Lancet Neurology, 19(11), 940–950.

    Article  CAS  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. Annual New York Academy of Sciences, 1139, 118–126.

    Article  CAS  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.

    Article  CAS  PubMed  Google Scholar 

  • Larsen, K. E., Fon, E. A., Hastings, T. G., Edwards, R. H., & Sulzer, D. (2002). Methamphetamine-induced degeneration of dopaminergic neurons involves autophagy and upregulation of dopamine synthesis. Journal of Neuroscience, 22(20), 8951–8960.

    Article  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, 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 

  • 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 

  • Lyles, J., & Cadet, J. L. (2003). Methylenedioxymethamphetamine (MDMA, ecstasy) neurotoxicity: Cellular and molecular mechanisms. 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 & Biobehavioral Reviews, 27(8), 821–826.

    Article  CAS  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.

    Article  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. The Journal of Pharmacology and Experimental Therapeutics, 340(2), 295–303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mithoefer, M. C., Mithoefer, A. T., Feduccia, A. A., Jerome, L., Wagner, M., Wymer, J., Holland, J., Hamilton, S., Yazar-Klosinski, B., Emerson, A., & Doblin, R. (2018). 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: A randomised, double-blind, dose-response, phase 2 clinical trial. Lancet Psychiatry, 5, 486–497.

    Article  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 

  • Mohammad Ahmadi Soleimani, S., Ekhtiari, H., & Cadet, J. L. (2016). Drug-induced neurotoxicity in addiction medicine: From prevention to harm reduction. Progress in Brain Research, 223, 19–41.

    Article  CAS  PubMed  Google Scholar 

  • Mulvihill, K. G. (2019). Presynaptic regulation of dopamine release: Role of the DAT and VMAT2 transporters. Neurochemistry International, 122, 94–105.

    Article  CAS  PubMed  Google Scholar 

  • Nixon, R. A., & Yang, D. S. (2011). Autophagy failure in Alzheimer’s disease–locating the primary defect. Neurobiology of Disease, 43(1), 38–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • O’Callaghan, J. P., & Miller, D. B. (1994). Neurotoxicity profiles of substituted amphetamines in the C57BL/6J mouse. The 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 

  • Pérez-Hernández, M., Fernández-Valle, M. E., Rubio-Araiz, A., Vidal, R., Gutiérrez-López, M. D., O’Shea, E., & Colado, M. I. (2017). 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) produces edema due to BBB disruption induced by MMP-9 activation in rat hippocampus. Neuropharmacology, 118, 157–166.

    Article  PubMed  Google Scholar 

  • Proebstl, L., Kamp, F., Koller, G., & Soyka, M. (2018). Cognitive deficits in methamphetamine users: How strong is the evidence? Pharmacopsychiatry, 51(6), 243–250.

    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 

  • Punja, S., Shamseer, L., Hartling, L., Urichuk, L., Vandermeer, B., Nikles, J., & Vohra, S. (2016). Amphetamines for attention deficit hyperactivity disorder (ADHD) in children and adolescents. Cochrane Database of Systematic Reviews, 2, CD009996.

    Google Scholar 

  • Quarta, A., Berneman, Z., & Ponsaerts, P. (2020). Functional consequences of a close encounter between microglia and brain-infiltrating monocytes during CNS pathology and repair. Journal of Leukocyte Biology. https://doi.org/10.1002/JLB.3RU0820-536R

  • Radi, E., Formichi, P., Battisti, C., & Federico, A. (2014). Apoptosis and oxidative stress in neurodegenerative diseases. Journal of Alzheimers Disease, 42(Suppl 3), S125–S152.

    Article  Google Scholar 

  • Raineri, M.,* Gonzalez, B.,* Goitia, B., Garcia-Rill, E., Cadet, J. L., Krasnova, I. N., Urbano, F. J., & Bisagno, V. (2012). Modafinil abrogates methamphetamine-induced neuroinflammation and apoptotic effects in the mouse striatum. PLoS One, 7, 1–10. *Authors contributed equally.

    Google Scholar 

  • Raineri, M., González, B., Rivero-Echeto, C., Muñiz, J. A., Gutiérrez, M. L., Ghanem, C. I., Cadet, J. L., García-Rill, E., Urbano, F. J., & Bisagno, V. (2015). Differential effects of environment-induced changes in body temperature on modafinil’s actions against methamphetamine-induced striatal toxicity in mice. Neurotoxicity Research, 1, 71–83.

    Article  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 

  • 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 

  • Rodríguez-Gómez, J. A., Kavanagh, E., Engskog-Vlachos, P., Engskog, M. K. R., Herrera, A. J., Espinosa-Oliva, A. M., Joseph, B., Hajji, N., Venero, J. L., & Burguillos, M. A. (2020). Microglia: Agents of the CNS pro-inflammatory response. Cell, 9(7), 1717.

    Article  Google Scholar 

  • Roohbakhsh, A., Shirani, K., & Karimi, G. (2016). Methamphetamine-induced toxicity: The role of autophagy? Chemico-Biological Interactions, 260, 163–167.

    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.

    Article  CAS  Google Scholar 

  • Saunders, J. B. (2017). Substance use and addictive disorders in DSM-5 and ICD 10 and the draft ICD 11. Current Opinion in Psychiatry, 30(4), 227–237.

    Article  PubMed  Google Scholar 

  • Schweppe, C. A., Burzynski, C., Jayanthi, S., Ladenheim, B., Cadet, J. L., Gardner, E. L., Xi, Z. X., van Praag, H., Newman, A. H., & Keck, T. M. (2020). Neurochemical and behavioral comparisons of contingent and non-contingent methamphetamine exposure following binge or yoked long-access self-administration paradigms. Psychopharmacology (Berlin), 237(7), 1989–2005.

    Article  CAS  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. American Journal of Psychiatry, 160, 1699–1701.

    Article  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  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 

  • Simpson, D. S. A., & Oliver, P. L. (2020). ROS generation in microglia: Understanding oxidative stress and inflammation in neurodegenerative disease. Antioxidants (Basel), 9(8), 743.

    Article  CAS  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  Google Scholar 

  • Subu, R., Jayanthi, S., & Cadet, J. L. (2020). Compulsive methamphetamine taking induces autophagic and apoptotic markers in the rat dorsal striatum. Archives of Toxicology. https://doi.org/10.1007/s00204-020-02844-w

  • Sulzer, D., Pothos, E., Sung, H. M., Maidment, N. T., Hoebel, B. G., & Rayport, S. (1992). Weak base model of amphetamine action. Annals of the New York Academy of Sciences, 654, 525–528.

    Article  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. (2011). How addictive drugs disrupt presynaptic dopamine neurotransmission. Neuron, 69, 628–649.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Teng, L., Crooks, P. A., & Dwoskin, L. P. (1998). Lobeline displaces [3H]dihydrotetrabenazine binding and releases [3H]dopamine from rat striatal synaptic vesicles: Comparison with d-amphetamine. Journal of Neurochemistry, 71, 258–265.

    Article  CAS  PubMed  Google Scholar 

  • Thanos, P. K., Kim, R., Delis, F., Ananth, M., Chachati, G., Rocco, M. J., Masad, I., Muniz, J. A., Grant, S. C., Gold, M. S., Cadet, J. L., & Volkow, N. D. (2016). Chronic methamphetamine effects on brain structure and function in rats. PLoS One, 11(6), e0155457. Erratum in: PLoS One. 2017 12 (2):e0172080.

    Article  PubMed  PubMed Central  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  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  Google Scholar 

  • Thorpy, M. J., & Bogan, R. K. (2020). Update on the pharmacologic management of narcolepsy: Mechanisms of action and clinical implications. Sleep Medicine, 68, 97–109.

    Article  PubMed  Google Scholar 

  • Umek, N., Geršak, B., Vintar, N., Šoštarič, M., & Mavri, J. (2018). Dopamine autoxidation is controlled by acidic pH. Frontiers in Molecular Neuroscience, 11, 467.

    Article  CAS  PubMed  PubMed Central  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 the International Neuropsychological Society, 12(3), 405–415.

    Article  PubMed  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.

    Article  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. 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. American Journal of Psychiatry, 158, 377–382.

    Article  CAS  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. American Journal of Psychiatry, 161(2), 242–248.

    Article  Google Scholar 

  • Xi, Z. X., Kleitz, H. K., Deng, X., Ladenheim, B., Peng, X. Q., Li, X., Gardner, E. L., Stein, E. A., & Cadet, J. L. (2009). A single high dose of methamphetamine increases cocaine self-administration by depletion of striatal dopamine in rats. Neuroscience, 161, 392–402.

    Article  CAS  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  PubMed Central  Google Scholar 

  • Yang, T., Zang, S., Wang, Y., Zhu, Y., Jiang, L., Chen, X., Zhang, X., Cheng, J., Gao, R., Xiao, H., & Wang, J. (2020). Methamphetamine induced neuroinflammation in mouse brain and microglial cell line BV2: Roles of the TLR4/TRIF/Peli1 signaling axis. Toxicology Letters, 333, 150–158.

    Article  CAS  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  Google Scholar 

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  1. Instituto de Investigaciones Farmacológicas (ININFA-UBA-CONICET), Buenos Aires, Argentina

    Verónica Bisagno

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

    Jean Lud Cadet

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

    Richard M. Kostrzewa

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Bisagno, V., Cadet, J.L. (2021). Methamphetamine and MDMA Neurotoxicity: Biochemical and Molecular Mechanisms. In: Kostrzewa, R.M. (eds) Handbook of Neurotoxicity. Springer, Cham. https://doi.org/10.1007/978-3-030-71519-9_80-1

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