In vivo evidence for low striatal vesicular monoamine transporter 2 (VMAT2) availability in cocaine abusers
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OBJECTIVE: Positron emission tomography (PET) imaging studies in cocaine abusers have shown that low dopamine release in the striatum following an amphetamine challenge is associated with higher relapse rates. One possible mechanism that might lead to lower amphetamine-induced dopamine release is low availability of dopamine storage vesicles in the presynaptic terminals for release. Consistent with this hypothesis, postmortem studies have shown low levels of vesicular monoamine transporter, type 2 (VMAT2), the membrane protein that regulates the size of the vesicular dopamine pool, in cocaine abusers relative to healthy subjects. To confirm the postmortem findings, the authors used PET and the VMAT2 radioligand [¹¹C]-(+)-dihydrotetrabenazine (DTBZ) to assess the in vivo VMAT2 availability in a group of 12 recently abstinent cocaine-dependent subjects and matched healthy comparison subjects. METHOD: [¹¹C]DTBZ nondisplaceable binding potential (BP(ND)) was measured by kinetic analysis using the arterial input function or, if arterial input was unavailable, by the simplified reference tissue method. RESULTS: [¹¹C]DTBZ BP(ND) was significantly lower in the cocaine abusers than in the comparison subjects in the limbic striatum (10.0% lower), associative striatum (-13.4%), and sensorimotor striatum (-11.5%). CONCLUSIONS: The results of this in vivo PET study confirm previous in vitro reports of low VMAT2 availability in the striatum of cocaine abusers. It also suggests a compensatory down-regulation of the dopamine storage vesicles in response to chronic cocaine abuse and/or a loss of dopaminergic terminals. Further research is necessary to understand the clinical relevance of this observation to relapse and outcome in abstinent cocaine abusers.
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Cocaine abuse is associated with decreased [18F]DOPA uptake and striatal VMAT2 binding.
“Cocaine abuse is associated with both decreased [18F]DOPA uptake and striatal vesicular monoamine transporter 2 (VMAT2) binding, which provide measures of pre-synaptic dopamine (Narendran et al., 2012; Wu et al., 1997).”
From Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity (2014) · cites this paper as Narendran et al., 2012
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- Authors
- Narendran, R., Lopresti, B. J., Martinez, D., Mason, N. S., Himes, M., May, M. A., Daley, D. C., Price, J. C., Mathis, C. A., & Frankle, W. G.
- Affiliations
- University of Pittsburgh (US)
- From the Departments of Radiology and Psychiatry, University of Pittsburgh; and the Department of Psychiatry, Columbia University Medical Center, New York.
- ORCID
- Venue
- American Journal of Psychiatry
- Published
- 2012-01
- Volume
- 169
- Issue
- 1
- Pages
- 55-63
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC3405490
- OpenAlex
- W2112032964
- Cited by
- 53
- References
- 38
- Citations by year
- 2026: 2 · 2025: 1 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 7 · 2019: 3 · 2018: 2 · 2017: 4 · 2016: 4 · 2015: 7 · 2014: 10 · 2013: 6 · 2012: 1
- FWCI
- 2.25
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Georgia Clinical and Translational Science Alliance (UL‐1 RR024153)
- National Institutes of Health (RR024153)
- National Institute on Drug Abuse (R03DA024704)
- National Center for Research Resources (RR-024153, UL1RR024153)
- 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
- cocaine dependence, vesicular monoamine transporter 2, striatum, [11C]dihydrotetrabenazine, dopamine release, relapse, dopaminergic terminals, striatal subregions
- MeSH terms
- Adult, Corpus Striatum, Female, Humans, Male, Tetrabenazine, Case-Control Studies, Cocaine-Related Disorders, Positron-Emission Tomography, Vesicular Monoamine Transport Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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