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Imaging Synaptic Neurotransmission with in Vivo Binding Competition Techniques: A Critical Review
Open accessAbstract
Several groups have provided evidence that positron emission tomography (PET) and single-photon emission computed tomography (SPECT) neuroreceptor imaging techniques might be applied to measure acute fluctuations in dopamine (DA) synaptic concentration in the living human brain. Competition between DA and radioligands for binding to D2 receptor is the principle underlying this approach. This new application of neuroreceptor imaging provides a dynamic measurement of neurotransmission that is likely to be informative to our understanding of neuropsychiatric conditions. This article reviews and discusses the body of data supporting the feasibility and potential of this imaging paradigm. Endogenous competition studies performed in rodents, nonhuman primates, and humans are first summarized. After this overview, the validity of the model underlying the interpretation of these imaging data is critically assessed. The current reference model is defined as the occupancy model, since changes in radiotracer binding potential (BP) are assumed to be directly caused by changes in occupancy of D2 receptors by DA. Experimental data supporting this model are presented. The evidence that manipulation of DA synaptic levels induces change in the BP of several D2 radiotracers (catecholamines and benzamides) is unequivocal. The fact that these changes in BP are mediated by changes in DA synaptic concentration is well documented. The relationship between the magnitude of BP changes measured with PET or SPECT and the magnitude of changes in DA concentration measured by microdialysis supports the use of these noninvasive techniques to measure changes in neurotransmission. On the other hand, several observations remain unexplained. First, the amphetamine-induced changes in the BP of D2 receptor antagonists [123I]IBZM and [11C]raclopride last longer than amphetamine-induced changes in DA extracellular concentration. Second, nonbenzamide D2 receptor antagonists, such as spiperone and pimozide, are not affected by changes in DA release, or are affected in a direction opposite to that predicted by the occupancy model. Similar observations are reported with D1 radiotracers. These results suggest that the changes in BP following changes in DA concentration might not be fully accounted by a simple occupancy model. Specifically, the data are reviewed supporting that agonist-mediated receptor internalization might play an important role in characterizing receptor-ligand interactions. Finally, it is proposed that a better understanding of the mechanism underlying the effects observed with benzamides is essential to develop this imaging technique to other receptor systems.
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“Consequently, we were not able to assess whether dynamics such as receptor internalization (Laruelle, 2000) or changes in the affinity of D2/D3 receptors for dopamine and/or fallypride were implicated (Laruelle, 2000; Gjedde et al., 2005).”
From A positron emission tomography study of nigro-striatal dopaminergic mechanisms underlying attention: implications for ADHD and its treatment (2013) · cites this paper as Laruelle, 2000
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Metadata
- Authors
- Laruelle, M.
- Affiliations
- New York State Psychiatric Institute (US)
- Corresponding author
- Laruelle, Marc
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 2000-03
- Volume
- 20
- Issue
- 3
- Pages
- 423-451
- ISSN
- 0271-678X (ISSN-L)
- 1559-7016
- OpenAlex
- W2054230322
- Cited by
- 944
- References
- 207
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 8 · 2023: 10 · 2022: 15 · 2021: 26 · 2020: 18 · 2019: 28 · 2018: 26 · 2017: 31 · 2016: 31 · 2015: 36 · 2014: 54 · 2013: 47 · 2012: 36
- FWCI
- 4.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (K02MH01603-01, K02MH001603)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- dopamine D2 receptor, competitive binding, occupancy models, dopamine release, amphetamine, benzamide, receptor internalization, dopamine D1 receptor, microdialysis, SPECT
- MeSH terms
- Animals, Binding, Competitive, Brain, Dopamine, Humans, Ligands, Models, Neurological, Synaptic Transmission, Receptors, Dopamine, Tomography, Emission-Computed, Tomography, Emission-Computed, Single-Photon
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