Lower prefrontal cortical synaptic vesicle binding in cocaine use disorder: An exploratory 11 C‐UCB‐J positron emission tomography study in humans
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Preclinical studies have revealed robust and long‐lasting alterations in dendritic spines in the brain following cocaine exposure. Such alterations are hypothesized to underlie enduring maladaptive behaviours observed in cocaine use disorder (CUD). The current study explored whether synaptic density is altered in CUD. Fifteen individuals with DSM‐5 CUD and 15 demographically matched healthy control (HC) subjects participated in a single 11 C‐UCB‐J positron emission tomography scan to assess density of synaptic vesicle glycoprotein 2A (SV2A). The volume of distribution ( V T ) and the plasma‐free fraction‐corrected form of the total volume of distribution ( V T /f P ) were analysed in the anterior cingulate cortex (ACC), dorsomedial and ventromedial prefrontal cortex (PFC), lateral and medial orbitofrontal cortex (OFC) and ventral striatum. A significant diagnostic‐group‐by‐region interaction was observed for V T and V T /f P . Post hoc analyses revealed no differences on V T , while for V T / f P showed lower values in CUD as compared with HC subjects in the ACC (−10.9%, p = 0.02), ventromedial PFC (−9.9%, p = 0.02) and medial OFC (−9.9%, p = 0.04). Regional V T / f P values in CUD, though unrelated to measures of lifetime cocaine use, were positively correlated with the frequency of recent cocaine use ( p = 0.02–0.03) and negatively correlated with cocaine abstinence ( p = 0.008–0.03). These findings provide initial preliminary in vivo evidence of altered (lower) synaptic density in the PFC of humans with CUD. Cross‐sectional variation in SV2A availability as a function of recent cocaine use and abstinence suggests that synaptic density may be dynamically and plastically regulated by acute cocaine, an observation that merits direct testing by studies using more definitive longitudinal designs.
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The use of VTs makes the study results more easily comparable to other [11C]UCB-J PET studies on related topics.
“The use of VTs also make our results more easily comparable to other [11C]UCB-J PET studies on related topics [20–23, 53, 57, 58].”
From Effects of escitalopram on synaptic density in the healthy human brain: a randomized controlled trial (2023) · cites this paper as [53]
A study on SV2A binding in cocaine-use disorder found a negative correlation between [11C]UCB-J binding and duration of cocaine abstinence, whereas years of lifetime use was unrelated to SV2A binding.
“A study on SV2A binding in cocaine-use disorder by Angarita et al. [53] found a negative correlation between [11C]UCB-J binding and duration of cocaine abstinence, whereas years of lifetime use was unrelated to SV2A binding.”
From Effects of escitalopram on synaptic density in the healthy human brain: a randomized controlled trial (2023) · cites this paper as [53]
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- Authors
- Angarita, G. A., Worhunsky, P. D., Naganawa, M., Toyonaga, T., Nabulsi, N. B., Li, C. R., Esterlis, I., Skosnik, P. D., Radhakrishnan, R., Pittman, B., Gueorguieva, R., Potenza, M. N., Finnema, S. J., Huang, Y., Carson, R. E., & Malison, R. T.
- Affiliations
- Yale University (US)
- Corresponding author
- Angarita, Gustavo A.
- ORCID
- Venue
- Addiction Biology
- Publisher
- Wiley
- Published
- 2021-12
- Volume
- 27
- Issue
- 2
- Pages
- e13123-e13123
- ISSN
- 1355-6215 (ISSN-L)
- 1369-1600
- PMC
- PMC8891080
- OpenAlex
- W3216040517
- Cited by
- 38
- References
- 75
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 8 · 2023: 10 · 2022: 6
- FWCI
- 2.77
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Addiction Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- State of Connecticut Department of Mental Health and Addiction Services
- National Center for Advancing Translational Sciences (UL1TR000142)
- Vetenskapsrådet
- Dana Foundation
- Nancy Taylor Foundation for Chronic Diseases
- National Institute on Drug Abuse (K01DA042998, R21DA044005)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- cocaine dependence, synaptic density, SV2A, prefrontal cortex, anterior cingulate cortex, orbitofrontal cortex, ventromedial prefrontal cortex, ventral striatum, dendritic spines, cocaine abstinence, synaptic plasticity
- MeSH terms
- Brain, Cocaine, Humans, Nerve Tissue Proteins, Pyridines, Synaptic Vesicles, Prefrontal Cortex, Positron-Emission Tomography
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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