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Dopamine depletion results in increased neostriatal D2, but not D1, receptor binding in humans

Molecular Psychiatry volume 7, pages 322–328 (2002)Cite this article

Abstract

The effect of endogenous dopamine (DA) on neostriatal DA D1 and D2 receptor binding potentials (D1RBP and D2RBP, respectively) in vivo was evaluated with positron emission tomography (PET) and the radiotracers [11C]SCH23390 and [11C]raclopride, respectively, by comparing the D1RBP and D2RBP before and after acute DA depletion. DA depletion was achieved by per-oral administration of 4500 mg α-methyl-para-tyrosine (AMPT) given in the 25 h prior to [11C]SCH23390 PET and of 5250 mg AMPT given in the 29 h prior to [11C]raclopride PET. Six healthy subjects completed the protocol. The AMPT treatment decreased plasma levels of the DA metabolite homovanillic acid by 61 ± 16% (4500 mg; average ± standard deviation) and 62 ± 17% (5250 mg), and levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenethyleneglycol by 58 ± 7% (4500 mg) and 66 ± 5% (5250 mg). This AMPT treatment increased D2RBP significantly from 3.18 ± 0.34 to 3.59 ± 0.30 but no significant change was observed in D1RBP (1.64 ± 0.24 pre AMPT vs 1.70 ± 0.17 post AMPT). Thus, while DA depletion ‘uncovers’ D2receptors, it does not do so for D1 receptors. The implications of this finding for measuring endogenous DA and its effects on in vivo receptor binding in humans are discussed.

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Acknowledgements

This work was supported by a Young Investigator Award from the National Alliance for Research on Schizophrenia and Affective Disorders to Dr Verhoeff, by a Postdoctoral Research Fellowship Award from the Ontario Mental Health Foundation to Dr Verhoeff, and by a grant from the Canadian Institute for Health Research to Dr Kapur. The authors gratefully acknowledge Merck & Co, West Point, Pennsylvania, USA, and Merck Frosst Canada, Point-Claire, Dorval, Quebec, Canada, for providing the AMPT; Cyrill Burger, PET Center, Division of Nuclear Medicine, University Hospital, Zürich, Switzerland, for providing the JAVA-based dedicated software PMOD; Terry Bell and Kevin Cheung for assistance in PET data acquisition; Corey Jones for his assistance with the preparation of the two figures; and staff of the Clinical Investigation Unit, 10th floor, Clarke Division, Centre for Addiction and Mental Health, for support for and management of the subjects during their overnight stay in the psychiatric inpatient unit.

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Authors and Affiliations

  1. Kunin-Lunenfeld Applied Research Unit, Baycrest Centre for Geriatric Care, Toronto, Ontario, Canada

    N P L G Verhoeff

  2. PET Centre, University of Toronto, Toronto, Ontario, Canada

    N P L G Verhoeff, D Hussey, J Tauscher, A A Wilson, S Houle & S Kapur

  3. Schizophrenia and Continuing Care Division, University of Toronto, Toronto, Ontario, Canada

    N P L G Verhoeff, J Tauscher, G Papatheodorou & S Kapur

  4. Psychopharmacology Research Laboratory, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada

    M Lee

  5. Department of General Psychiatry, University of Vienna, Vienna, Austria

    J Tauscher

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Correspondence to N P L G Verhoeff.

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Verhoeff, N., Hussey, D., Lee, M. et al. Dopamine depletion results in increased neostriatal D2, but not D1, receptor binding in humans. Mol Psychiatry 7, 322–328 (2002). https://doi.org/10.1038/sj.mp.4001057

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