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Cited by 1,291Schizophrenia research and treatmentNeurotransmitter Receptor Influence on BehaviorParkinson's Disease Mechanisms and Treatments

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Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects

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Laruelle, M, Abi-Dargham, A, van Dyck, C H, Gil, R, D'Souza, C D, Erdos, J, McCance, E, Rosenblatt, W, Fingado, C, Zoghbi, S S, Baldwin, R M, Seibyl, J P, Krystal, J H, Charney, D S, Innis, R B·1996·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.93.17.9235PMC PMC38625
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Abstract

The dopamine hypothesis of schizophrenia proposes that hyperactivity of dopaminergic transmission is associated with this illness, but direct observation of abnormalities of dopamine function in schizophrenia has remained elusive. We used a newly developed single photon emission computerized tomography method to measure amphetamine-induced dopamine release in the striatum of fifteen patients with schizophrenia and fifteen healthy controls. Amphetamine-induced dopamine release was estimated by the amphetamine-induced reduction in dopamine D2 receptor availability, measured as the binding potential of the specific D2 receptor radiotracer [123I] (S)-(-)-3-iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl) methyl]benzamide ([123I]IBZM). The amphetamine-induced decrease in [123I]IBZM binding potential was significantly greater in the schizophrenic group (-19.5 +/- 4.1%) compared with the control group (-7.6 +/- 2.1%). In the schizophrenic group, elevated amphetamine effect on [123I]IBZM binding potential was associated with emergence or worsening of positive psychotic symptoms. This result suggests that psychotic symptoms elicited in this experimental setting in schizophrenic patients are associated with exaggerated stimulation of dopaminergic transmission. Such an observation would be compatible with an abnormal responsiveness of dopaminergic neurons in schizophrenia.

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Authors
Laruelle, M., Abi-Dargham, A., van Dyck, C. H., Gil, R., D'Souza, C. D., Erdos, J., McCance, E., Rosenblatt, W., Fingado, C., Zoghbi, S. S., Baldwin, R. M., Seibyl, J. P., Krystal, J. H., Charney, D. S., & Innis, R. B.
Affiliations
  • Yale University (US)
  • Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06520, USA.
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
1996-08-20
Volume
93
Issue
17
Pages
9235-9240
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.93.17.9235
PMC
PMC38625
OpenAlex
W1996327177
Cited by
1,291
References
3
Citations by year
2026: 12 · 2025: 16 · 2024: 25 · 2023: 26 · 2022: 17 · 2021: 19 · 2020: 31 · 2019: 33 · 2018: 26 · 2017: 38 · 2016: 36 · 2015: 44 · 2014: 57 · 2013: 58 · 2012: 65
FWCI
23.33
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Veterans Affairs
  • Yale University
  • National Alliance for Research on Schizophrenia and Depression
  • U.S. Public Health Service
  • National Institute of Mental Health (MH-54192, R01MH054192)
  • National Center for Research Resources (M01RR000125, M01 RR-00125)
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, dopamine release, amphetamine challenge, dopamine D2 receptor, [123I]IBZM, striatum, dopamine hypothesis of schizophrenia, positive psychotic symptoms, dopamine signaling, SPECT imaging
MeSH terms
Adult, Amphetamine, Animals, Benzamides, Corpus Striatum, Dopamine, Female, Humans, Male, Papio, Psychoses, Substance-Induced, Pyrrolidines, Schizophrenia, Tomography, Emission-Computed, Single-Photon, Receptors, Dopamine D2, Dopamine Antagonists

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