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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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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