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Reduced Striatal Dopamine Transporter Density in Abstinent Methamphetamine and Methcathinone Users: Evidence from Positron Emission Tomography Studies with [11C]WIN-35,428
Open accessAbstract
Methamphetamine and methcathinone are psychostimulant drugs with high potential for abuse. In animals, methamphetamine and related drugs are known to damage brain dopamine (DA) neurons, and this damage has recently been shown to be detectable in living nonhuman primates by means of positron emission tomography (PET) with [11C]WIN-35,428, a DA transporter (DAT) ligand. The present studies determined whether living humans with a history of methamphetamine or methcathinone abuse showed evidence of lasting decrements in brain DAT density. PET studies were performed in 10 control subjects, six abstinent methamphetamine users, four abstinent methcathinone users, and three patients with Parkinson's disease (PD). On average, subjects had abstained from amphetamine use for approximately 3 years. Before PET studies, all subjects underwent urine and blood toxicology screens to rule out recent drug use. Compared with controls, abstinent methamphetamine and methcathinone users had significant decreases in DAT density in the caudate nucleus (-23 and -24%, respectively) and putamen (-25 and -16%, respectively). Larger decreases in DAT density were evident in patients with PD (47 and 68% in caudate and putamen, respectively). Neither methamphetamine nor methcathinone users showed clinical signs of parkinsonism. Persistent reductions of DAT density in methamphetamine and methcathinone users are suggestive of loss of DAT or loss of DA terminals and raise the possibility that as these individuals age, they may be at increased risk for the development of parkinsonism or neuropsychiatric conditions in which brain DA neurons have been implicated.
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“Alternatively, studies in methamphetamine abusers show a consistent and long lasting decrease in the dopamine transporter, which is the main target of this drug (Chou et al., 2007; Johanson et al., 2006; McCann et al., 1998; McCann et al., 2008; Sekine et al., 2001; Volkow et al., 2001b).”
From Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity (2014) · cites this paper as McCann et al., 1998
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Citations
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“N IH -PA Author M anuscript N IH -PA Author M anuscript cortex, caudate and putamen (McCann et al., 1998, 2008; Volkow et al., 2001) as well as serotonin transporters (Sekine et al., 2006).”
Zhou, J., Deng, W., Chen, C., Kang, J., Yang, X., Dou, Z., Wu, J., Li, Q., Jiang, M., Liang, M., et al. (2022) · Neuroscience Bulletin · doi:10.1007/s12264-022-00965-z · Cited by 6
“1 3 tomography studies suggested that dopamine transporter density is significantly reduced in chronic MCAT and methamphetamine users, and this is an expected consequence in drug abuse, suggesting functional regulation of the dopaminergic system [5].”
BackgroundGranado, N., Mendieta, L., Tizabi, Y., Murer, M. G., & Moratalla, R. (2025) · Neurobiology of Disease · doi:10.1016/j.nbd.2025.106839 · Cited by 6
“Similarly, METH users exhibit long-lasting reductions in striatal DA levels and DAT binding (Jayanthi et al., 2021; Kish et al., 2017; McCann et al., 1998, 2008; Sekine et al., 2001; Volkow et al., 2001a, 2001b, 2015; Wilson et al., 1996), as well as reduced D2-type receptor binding in the striatum…”
Influence of Methylenedioxypyrovalerone on Central Nervous System -Using Microdialysis Method-
Fuwa, T., Kodama, T., Honda, Y., Tanaka, T., Kubo, Y., Ohashi, N., Nakae, D., & Ogat, A. (2009) · Cited by 6
The emergence of cardiac changes following the self-administration of methamphetamine
Freeling, J., & McFadden, L. M. (2020) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2020.108029 · Cited by 6
Alsanie, W. F., Abdelrahman, S., Felimban, R. I., Alkhatabi, H. A., Gaber, A., Alosimi, E. A., Alhomrani, M., Habeeballah, H. H., Hauser, C. A. E., Alamri, A. S., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065668 · Cited by 6
Urigüen, L., & Callado, L. F. (2010) · Trastornos Adictivos · doi:10.1016/s1575-0973(10)70025-8 · Cited by 8
The Neuropathology of Drug Abuse
Büttner, A. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-418679-8.00007-1 · Cited by 7
Connolly, N. P., & Gomez-Serrano, M. (2014) · Experimental and Clinical Psychopharmacology · doi:10.1037/a0038216 · Cited by 6
Zhao, W., Zhao, Y., Ming, L., Liu, L., & Wang, Y. (2021) · Molecular Biology Reports · doi:10.1007/s11033-021-06741-y · Cited by 6
Fischman, A. J., & Badgaiyan, R. D. (2006) · Springer eBooks · doi:10.1007/0-387-34641-4_21 · Cited by 6
Provencher, B. A., Eshleman, A. J., Johnson, R. A., Shi, X., Kryatova, O. P., Nelson, J. K., Jianhua, T., Gonzalez, M., Meltzer, P. C., & Janowsky, A. J. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00542 · Cited by 6
Developments in the treatment of drug dependence
Bobes, J., & McCann, U. D. (2000) · Current Opinion in Psychiatry · doi:10.1097/00001504-200005000-00016 · Cited by 6
Acute effects of methcathinone and manganese in mice: A dose response study
Asser, A., Kõks, S., Soomets, U., Terasmaa, A., Sauk, M., Eltermaa, M., Piip, P., Ubhayasekera, K. A., Bergquist, J., & Taba, P. (2019) · Heliyon · doi:10.1016/j.heliyon.2019.e02475 · Cited by 6
Lin, S., Chen, K. C., Lee, S.-Y., Chiu, N.-T., Lee, I. H., Chen, P. S., Yeh, T. L., Lu, R., Chen, C., Liao, M., et al. (2015) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2015.01.011 · Cited by 5
Inflammatory mechanisms of abused drugs
Mitchell, C. M., Jordi, O. E., & Yamamoto, B. K. (2018) · Advances in neurotoxicology · doi:10.1016/bs.ant.2018.10.006 · Cited by 5
Use of illicit amphetamines is associated with long-lasting changes in hand circuitry and control
Pearson-Dennett, V., Faulkner, P. L., Collie, B., Wilcox, R. A., Vogel, A. P., Thewlis, D., Esterman, A., McDonnell, M. N., Gandevia, S. C., White, J. M., et al. (2019) · Clinical Neurophysiology · doi:10.1016/j.clinph.2019.02.005 · Cited by 5
Garavan, H., Lingford-Hughes, A. R., Jones, T., Morris, P. G., Rothwell, J. C., & Williams, S. (2007) · Elsevier eBooks · doi:10.1016/b978-012370624-9/50012-8 · Cited by 5
1 Central nervous system stimulants and drugs that suppress appetite
Sequeira, R. P. (2007) · Side effects of drugs annual · doi:10.1016/s0378-6080(06)29001-9 · Cited by 5
Fricks-Gleason, A. N., German, C. L., Hoonakker, A. J., Friend, D. M., Ganesh, K., Carver, A. S., Hanson, G., Fleckenstein, A., & Keefe, K. (2016) · Synapse · doi:10.1002/syn.21891 · Cited by 6
“Persistent decreases in markers of DA innervation of the striatum have been reported among human METH abusers (McCann et al., 1998), and recent findings show that individuals with a history of hospitalization for METH abuse are more likely to develop Parkinson’s disease later in life (Callaghan et…”
BackgroundThe Dopamine Transporter: Molecular Biology, Pharmacology and Genetics
Pifl, C., & Caron, M. G. (2002) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-56051-4_10 · Cited by 5
Neuroimaging and mechanisms of drug abuse: interface of molecular imaging and molecular genetics
Monique Ernst, D., Kimes, A. S., & Jazbec, S. (2003) · Neuroimaging Clinics of North America · doi:10.1016/s1052-5149(03)00109-6 · Cited by 5
Methamphetamine and MDMA Neurotoxicity: Biochemical and Molecular Mechanisms
Bisagno, V., & Cadet, J. L. (2014) · Springer eBooks · doi:10.1007/978-1-4614-5836-4_80 · Cited by 5
Imaging of dopaminergic transmission in neuropsychiatric disorders
Verhoeff, N. (2001) · Current Opinion in Psychiatry · doi:10.1097/00001504-200105000-00011 · Cited by 6
Animal models of Parkinson’s disease and related disorders
Petzinger, G. M., & Jakowec, M. W. (2013) · CRC Press eBooks · doi:10.1201/b14361-17 · Cited by 4
Stepens, A., & Taba, P. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-800634-4.00091-3 · Cited by 4
Sikk, K. (2011) · Frontiers in Genetics · doi:10.3389/fgene.2011.00042 · Cited by 5
“However, methcathinone has a molecular structure similar to methamphetamine and its pharmacodynamic properties suggest potential toxicity as well (Glennon et al., 1995; Rockhold et al., 1997; McCann et al., 1998).”
BackgroundFang, H., Tong, W., Shi, L. M., Jakab, R. L., & Bowyer, J. F. (2004) · DNA and Cell Biology · doi:10.1089/1044549042476875 · Cited by 4
Lancia, A. J., Williams, E. A., McKnight, L. V., & Zahm, D. S. (2003) · Brain Research · doi:10.1016/j.brainres.2003.10.044 · Cited by 4
Baladi, M. G., Nielsen, S. M., McIntosh, J. M., Hanson, G. R., & Fleckenstein, A. E. (2016) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000215 · Cited by 4
Neurochemical Imaging of Addictive Disorders
Broft, A. I., & Martínez, D. (2012) · Neuromethods · doi:10.1007/7657_2012_48 · Cited by 4
Methamphetamine Neurotoxicity and Neuroinflammatory Processes
Northrop, N. A., & Yamamoto, B. K. (2014) · Springer eBooks · doi:10.1007/978-1-4939-1071-7_21 · Cited by 4
Grasing, K., Azevedo, R., Karuppan, S., & Ghosh, S. (2001) · Neurochemical Research · doi:10.1023/a:1007632700126 · Cited by 4
Nitric Oxide-Dependent Processes in the Action of Psychostimulants
Itzhak, Y., Martin, J. L., & Ali, S. F. (2002) · Humana Press eBooks · doi:10.1007/978-1-59259-306-4_15 · Cited by 4
Dopamine Receptors Gene Expression in Male Rat Hippocampus after Administration of MDMA (Ecstasy)
Simin, M., Jahanshahi, M., Haidari, K., & Shahbazi, M. (2015) · International Journal of Morphology · doi:10.4067/s0717-95022015000100048 · Cited by 3
“In similar research in vivo the decrease in the amount of Dopamine vectors among METH takers were reported (McCann et al., 1998).”
BackgroundMethcathinone decreases dopamine transporter function: Role of protein kinase C
Magee, C., Le, B. D., Siripathane, Y. H., Wilkins, D., Hanson, G., & Fleckenstein, A. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15483 · Cited by 3
Koob, G. F., Arends, M. A., McCracken, M. L., & Moal, M. L. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-816990-2.00001-6 · Cited by 4
Neurotoxicity in Psychostimulant and Opiate Addiction
Niedzielska, E., Rospond, B., Pomierny-Chamioło, L., Sadakierska−Chudy, A., & Filip, M. (2021) · Springer eBooks · doi:10.1007/978-3-030-71519-9_179-1 · Cited by 3
Neurotoxicity in Psychostimulant and Opiate Addiction
Niedzielska, E., Rospond, B., Pomierny-Chamioło, L., Sadakierska−Chudy, A., & Filip, M. (2014) · Springer eBooks · doi:10.1007/978-1-4614-5836-4_179 · Cited by 3
Metadata
- Authors
- McCann, U. D., Wong, D. F., Yokoi, F., Villemagne, V., Dannals, R. F., & Ricaurte, G. A.
- Affiliations
- National Institute of Mental Health (US)
- Johns Hopkins University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1998-10-15
- Volume
- 18
- Issue
- 20
- Pages
- 8417-8422
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6792853
- OpenAlex
- W2106287416
- Cited by
- 602
- References
- 46
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 8 · 2023: 12 · 2022: 10 · 2021: 19 · 2020: 11 · 2019: 12 · 2018: 14 · 2017: 16 · 2016: 16 · 2015: 27 · 2014: 32 · 2013: 38 · 2012: 34
- FWCI
- 8.18
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01da009482-05, 5r01da006275-03)
- National Institute of Mental Health
- National Institute on Drug Abuse (F32DA005707, DA05707, DA09482, DA-06275, R01DA005707)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- methamphetamine, methcathinone, amphetamine abuse, dopamine transporter density, striatum, caudate nucleus, putamen, dopamine neuron loss, Parkinson's disease, psychostimulants, neurotoxicity
- MeSH terms
- Adult, Central Nervous System Stimulants, Brain Chemistry, Carbon Radioisotopes, Carrier Proteins, Cocaine, Female, Humans, Male, Membrane Glycoproteins, Methamphetamine, Middle Aged, Nerve Tissue Proteins, Parkinson Disease, Secondary, Propiophenones, Tomography, Emission-Computed, Neostriatum, Dopamine Uptake Inhibitors, Amphetamine-Related Disorders, Membrane Transport Proteins, Dopamine Plasma Membrane Transport Proteins
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