Cited by 1,154Schizophrenia research and treatmentNeurotransmitter Receptor Influence on BehaviorParkinson's Disease Mechanisms and Treatments

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Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: Evidence from a novel positron emission tomography method

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Breier, A., Su, T.-P., Saunders, R., Carson, R. E., Kolachana, B. S., de Bartolomeis, A., Weinberger, D. R., Weisenfeld, N., Malhotra, A. K., Eckelman, W. C., Pickar, D.·1997·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.94.6.2569PMC PMC20129

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Abstract

A major line of evidence that supports the hypothesis of dopamine overactivity in schizophrenia is the psychomimetic potential of agents such as amphetamine that stimulate dopamine outflow. A novel brain imaging method provides an indirect measure of in vivo synaptic dopamine concentration by quantifying the change in dopamine receptor radiotracer binding produced by agents that alter dopamine release but do not themselves bind to dopamine receptors. The purpose of this investigation is (i) to determine the sensitivity (i.e., amount of dopamine reflected in radiotracer binding changes) of this method by examining the relationship between amphetamine-induced changes in simultaneously derived striatal extracellular dopamine levels with in vivo microdialysis and striatal binding levels with the dopamine D2/D3 positron-emission tomography radioligand [11C]raclopride in nonhuman primates, and (ii) to test the hypothesis of elevated amphetamine-induced synaptic dopamine levels in schizophrenia. In the nonhuman primate study (n = 4), doubling the amphetamine dose produced a doubling in [11C]raclopride specific binding reductions. In addition, the ratio of percent mean dopamine increase to percent mean striatal binding reduction for amphetamine (0.2 mg/kg) was 44:1, demonstrating that relatively small binding changes reflect large changes in dopamine outflow. In the clinical study, patients with schizophrenia (n = 11) compared with healthy volunteers (n = 12) had significantly greate…

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Disrupted relationship between blood glucose and brain dopamine D2/3 receptor binding in patients with first-episode schizophrenia
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“Patients with schizophrenia show striatal hyperactivity of dopaminergic function (12) and”
Background
Striatal dopamine D2/3 receptors in medication-naïve schizophrenia: an [123I] IBZM SPECT study
Chen, K.-C., Yang, Y.-K., Howes, O., Lee, H. I., Yeh, T.-L., Chiu, N.-T., Chen, P.-S., David, A., & Bramon, E. (2021) · Psychological Medicine · doi:10.1017/s0033291720005413 · Cited by 7
“Positive symptoms may be induced by the increased synaptic release of dopamine in the striatum (Breier et al., 1997; Buchsbaum et al., 2006; de Haan et al., 2004; McCutcheon, Beck, Jauhar, & Howes, 2018; Schmitt et al., 2008; Yang et al., 2004).”
Background
Impairment of motor but not anxiety‐like behavior caused by the increase of dopamine during development is sustained in zebrafish larvae at later stages
Lima, A. C. M. D. S., de Alvarenga, K. A. F., Codo, B. C., Sacramento, E. K., Rosa, D. V., de Souza, R. P., Romano‐Silva, M. A., & Souza, B. R. (2020) · International Journal of Developmental Neuroscience · doi:10.1002/jdn.10009 · Cited by 8
“Furthermore, brain imaging studies have shown that there is an increase of levels of presynaptic dopamine (DA), DA release, and the DAergic receptor D2 in the brains of schizophrenic patients (Breier et al., 1997; Howes & Kapur, 2009; Lindström et al., 1999; Reith et al., 1994; Wong et al., 1986).”
Background
Toward the Optimization of (+)-[11C]PHNO Synthesis: Time Reduction and Process Validation
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“binding to striatal D2 receptors as compared to control subjects (Laruelle et al., 1996; Breier et al., 1997).”
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PET and SPECT Imaging of the Central Dopamine System in Humans
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PET imaging of neurotransmission using direct parametric reconstruction
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“…and motivational functions in normal and neuropathological conditions, including substance abuse (Volkow et al., 1997; Cox et al., 2009; Busto et al., 2009; Martinez et al., 2005), schizophrenia (Breier et al., 1997; Abi-Dargham et al., 1998), Tourette’s syndrome (Singer et al., 2002;…”
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“A temporary increase of dopamine production has been demonstrated only during acute psychotic episodes (Abi-Dargham et al., 1999, 2000; Breier et al., 1997; Laruelle, Abi-Dargham, Gill, Kegeles, & Innis, 1999).”
Background
NeuroImaging bei schizophrenen Erkrankungen
Lanzenberger, R., & Kasper, S. (2005) · Fortschritte der Neurologie, Psychiatrie. SH/Fortschritte der Neurologie, Psychiatrie. Sonderheft · doi:10.1055/s-2005-915581 · Cited by 6
The Dopamine Hypothesis of Schizophrenia
Gründer, G., & Cumming, P. D. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-801829-3.00015-x · Cited by 57
Cocaine
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“candidate [13], or, 2.”
Self-citation
TAAR1 Regulates Presynaptic Dopamine Function: Evidence From Preclinical Studies and a Phase 1b Trial in Patients With Schizophrenia
Howes, O. D., Vano, L. J., Petty, A. E., Rutigliano, G., Halff, E. F., Veronese, M., Kaar, S. J., Nordio, G., Lopes, E. F., Cragg, S. J., et al. (2025) · Biological Psychiatry · doi:10.1016/j.biopsych.2025.10.013 · Cited by 8
Influence of the dose of ketamine used on schizophrenia-like symptoms in mice: A correlation study with TH, GAD67, and PPAR-γ
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The Effect of Chronic Methamphetamine Treatment on Schizophrenia Endophenotypes in Heterozygous Reelin Mice: Implications for Schizophrenia
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“In conclusion, chronic Meth treatment resulted in long-term enhancement of locomotor hyperactivity to an acute Meth challenge, reflecting sensitisation similar to that seen in schizophrenia [12,14,15,17,26].”
Background
Early postnatal l-Dopa treatment causes behavioral alterations in female vs. male young adult Swiss mice
de Matos, L. O., Reis, A. L. D. A. L., Guerra, L. T. L., Guarnieri, L. D. O., Moraes, M. A., Arabe, L. B., de Souza, R. P., Pereira, G. S., & Souza, B. R. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108047 · Cited by 5
In vivo imaging of D2 receptors and corticosteroids predict behavioural responses to captivity stress in a wild bird
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Self-citation
COMT genotype is associated with plasticity in sense of body ownership: a pilot study
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Potential Effect of Prolonged Sevoflurane Anesthesia on the Kinetics of [11C]Raclopride in Non-human Primates
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“Since it has been estimated that a 40 % increase in dopamine corresponds to a 1 % reduction of [(11)C]raclopride BPND [20, 21], a hypothetical change of BPND by sevoflurane should likely be negligible.”
Background
Striatal and extrastriatal dopamine release in the common marmoset brain measured by positron emission tomography and [18F]fallypride
Ota, M., Ogawa, S., Kato, K., Masuda, C., & Kunugi, H. (2015) · Neuroscience Research · doi:10.1016/j.neures.2015.07.008 · Cited by 5
“Subsequent studies have provided strong evidence for enhanced dopaminergic activity in schizophrenia, such that amphetamine-induced dopamine release was enhanced in the striatum (Laruelle et al., 1996; Breier et al., 1997; Abi-Dargham et al., 1998).”
Background
Neuroimaging of Treatment-Resistant Schizophrenia
Borgio, J. G. F., Rocha, D., Elkis, H., & Bressan, R. A. (2010) · Advances in biological psychiatry · doi:10.1159/000319809 · Cited by 3
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In Vivo Imaging of Dopamine Metabolism and Dopamine Transporter Function in the Human Brain
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“Introduction The utility of positron emission tomography (PET) for detecting net changes in endogenous neurotransmitters after a stimulus has already been demonstrated through a variety of approaches [1–9].”
Background

Authors: Breier, A., Su, T.-P., Saunders, R., Carson, R. E., Kolachana, B. S., de Bartolomeis, A., Weinberger, D. R., Weisenfeld, N., Malhotra, A. K., Eckelman, W. C., & Pickar, D.
Affiliations: National Institutes of Health (US)
ORCID: Su, T.-P.
Saunders, R.
Carson, R. E.
Kolachana, B. S.
de Bartolomeis, A.
Weinberger, D. R.
Malhotra, A. K.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1997-03-18
Volume: 94
Issue: 6
Pages: 2569-2574
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.94.6.2569
PMC: PMC20129
OpenAlex: W2150760506
Cited by: 1,154
References: 43
Citations by year: 2026: 8 · 2025: 12 · 2024: 19 · 2023: 9 · 2022: 17 · 2021: 22 · 2020: 20 · 2019: 26 · 2018: 29 · 2017: 27 · 2016: 34 · 2015: 35 · 2014: 44 · 2013: 51 · 2012: 54
FWCI: 36.57
Type: journal article
Language: en
Open access: green
europepmc.org
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
Keywords: schizophrenia, synaptic dopamine, amphetamine, [11C]raclopride, striatum, dopamine release, microdialysis, non-human primates
MeSH terms: Amphetamine, Animals, Carbon Radioisotopes, Corpus Striatum, Dopamine, Humans, Macaca mulatta, Reference Values, Regression Analysis, Salicylamides, Schizophrenia, Synapses, Tomography, Emission-Computed, Microdialysis, Raclopride

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Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: Evidence from a novel positron emission tomography method

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