Reduced Striatal Dopamine Transporter Density in Abstinent Methamphetamine and Methcathinone Users: Evidence from Positron Emission Tomography Studies with [11C]WIN-35,428
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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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Methamphetamine abusers show a consistent and long-lasting decrease in the dopamine transporter, the main target of methamphetamine.
“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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- 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 › 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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