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Imaging the Dopamine System with In Vivo [11C]raclopride Displacement Studies: Understanding the True Mechanism

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Abstract

Measuring changes in dopamine (DA) levels in humans using radioligand-displacement studies and positron emission tomography (PET) has provided important empirical findings in diseases and normal neurophysiology. These studies are based on the assumption that DA exerts a competitive inhibition on D2-radioligand binding. However, the transfer of this hypothesis to a proven mechanism has not been fully achieved yet and an accumulating number of studies challenge it. In addition, new evidence suggests that DA exerts a noncompetitive inhibition on D2-radioligand binding under amphetamine conditions. This article reviews the theoretical basis for the DA competition hypothesis, the in vivo and in vitro evidences supporting a noncompetitive action of DA on D2-radioligand binding under amphetamine conditions, and discusses possible mechanisms underlying this noncompetitive interaction. Finally, we propose that such noncompetitive interactions may have important implications for how one interprets findings obtained from radioligand-displacement PET studies in neuropsychiatric diseases, especially in schizophrenia in which a dysregulation of the DA-promoted internalization of D2 receptors was recently suggested.

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Acknowledgment

The author thanks Shitij Kapur, MD, PhD, for fruitful discussions during the preparation of this manuscript.

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  1. PET Centre, Centre for Addiction and Mental Health, University of Toronto, 250 College Street, M5T 1R8, Toronto, Ontario, Canada

    Nathalie Ginovart PhD

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Ginovart, N. Imaging the Dopamine System with In Vivo [11C]raclopride Displacement Studies: Understanding the True Mechanism. Mol Imaging Biol 7, 45–52 (2005). https://doi.org/10.1007/s11307-005-0932-0

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