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Cognitive function and nigrostriatal markers in abstinent methamphetamine abusers
Abstract
Objective Preclinical investigations have established that methamphetamine (MA) produces long-term changes in dopamine (DA) neurons in the striatum. Human studies have suggested similar effects and correlated motor and cognitive deficits. The present study was designed to further our understanding of changes in brain function in humans that might result from chronic high dose use of MA after at least 3 months of abstinence.Method Brain function in abstinent users was compared to controls using neuroimaging of monoamine transporters and cognitive assessment. Striatal levels of DA transporter (DAT) and vesicular monoamine transporter type-2 (VMAT2) were determined using [11C]methylphenidate and [11C]dihydrotetrabenazine positron emission tomography, respectively. Cognitive function was evaluated using tests of motor function, memory, learning, attention, and executive function.Results Striatal DAT was approximately 15% lower and VMAT2 was 10% lower in MA abusers across striatal subregions. The MA abusers performed within the normal range but performed more poorly compared to controls on three of the 12 tasks.Conclusions Failure to find more substantial changes in transporter levels and neurocognitive function may be attributed to the length of time that MA users were abstinent (ranging from 3 months to more than 10 years, mean 3 years), although there were no correlations with length of abstinence. Persistent VMAT2 reductions support the animal literature indicating a toxic effect of MA on nigrostriatal nerve terminals. However, the magnitude of the MA effects on nigrostriatal projection integrity is sufficiently small that it is questionable whether clinical signs of DA deficiency are likely to develop.
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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 Johanson et al., 2006
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Metadata
- Authors
- Johanson, C.-E., Frey, K. A., Lundahl, L. H., Keenan, P., Lockhart, N., Roll, J., Galloway, G. P., Koeppe, R. A., Kilbourn, M. R., Robbins, T., & Schuster, C. R.
- Affiliations
- Wayne State University (US)
- University of Michigan (US)
- Friends Research Institute (US)
- University of Cambridge (GB)
- Corresponding author
- Johanson, Chris-Ellyn
- ORCID
- Venue
- Psychopharmacology
- Published
- 2006-03-03
- Volume
- 185
- Issue
- 3
- Pages
- 327-338
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W1973774749
- Cited by
- 233
- References
- 49
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 5 · 2022: 7 · 2021: 11 · 2020: 30 · 2019: 8 · 2018: 9 · 2017: 12 · 2016: 11 · 2015: 15 · 2014: 12 · 2013: 19 · 2012: 21
- FWCI
- 4.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- Funders
- National Institutes of Health (5r01da012458-03, 5r21da014392-02)
- National Institute on Drug Abuse (DA14392, DA12458, R01DA010641, R01 DA10641)
- National Institute of Neurological Disorders and Stroke (NS-15655)
- National Center for Research Resources (RR00042, M01RR000042)
- 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, abstinence, cognitive function, nigrostriatal pathway, dopamine transporter, vesicular monoamine transporter 2, striatum, dopamine deficiency, monoamine transporters, executive function, learning and memory, attention, motor function
- MeSH terms
- Adolescent, Adult, Cognition, Corpus Striatum, Dopamine, Female, Humans, Male, Methamphetamine, Middle Aged, Psychological Tests, Substantia Nigra, Amphetamine-Related Disorders, Dopamine Plasma Membrane Transport Proteins, Vesicular Monoamine Transport Proteins
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