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    Regulation of dopaminergic function: an [F-18]-DOPA PET apomorphine challenge study in humans

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    17
    Author
    Jauhar, S; Veronese, M; Rogdaki, M; Bloomfield, M; Natesan, S; Turkheimer, F; Kapur, S; Howes, OD
    Date
    2017-02-07
    Source Title
    Translational Psychiatry
    Publisher
    NATURE PUBLISHING GROUP
    University of Melbourne Author/s
    Kapur, Shitij
    Affiliation
    Medicine Dentistry & Health Sciences
    Metadata
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    Document Type
    Journal Article
    Citations
    Jauhar, S., Veronese, M., Rogdaki, M., Bloomfield, M., Natesan, S., Turkheimer, F., Kapur, S. & Howes, O. D. (2017). Regulation of dopaminergic function: an [F-18]-DOPA PET apomorphine challenge study in humans. TRANSLATIONAL PSYCHIATRY, 7 (2), https://doi.org/10.1038/tp.2016.270.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/259043
    DOI
    10.1038/tp.2016.270
    Abstract
    Dopaminergic function has a key role in normal brain function, dopaminergic dysfunction being implicated in numerous neuropsychiatric disorders. Animal studies show that dopaminergic stimulation regulates dopaminergic function, but it is not known whether this exists in humans. In the first study (study 1), we measured dopamine synthesis capacity (indexed as Kicer) to identify the relationship between baseline and change in Kicer under resting conditions for comparison with effects of dopaminergic stimulation. In the second study (study 2), we used a within-subjects design to test effects of dopaminergic stimulation on dopamine synthesis capacity. In study 1, eight volunteers received two 18F-DOPA scans on separate days, both at rest. In study 2, 12 healthy male volunteers received two 18F-DOPA positron emission tomographic (PET) scans after treatment with either the dopamine partial agonist apomorphine (0.03 or 0.005 mg kg-1) or placebo. In study 1, no significant correlation was found between baseline and change in dopamine synthesis capacity between scans (r=-0.57, n=8, P=0.17, two-tailed). In study 2, a significant negative correlation was found between baseline dopamine synthesis capacity and percentage change in dopamine synthesis capacity after apomorphine challenge (r=-0.71, n=12, P=0.01, two-tailed). This correlation was significantly different (P<0.01) from the correlation between baseline and change in dopamine synthesis capacity under unstimulated conditions. One-way repeated-measures analysis of variance showed a significant group (study 1/study 2) × time interaction (F(1,18)=11.5, P=0.003). Our findings suggest that regulation of dopamine synthesis capacity by apomorphine depends on baseline dopamine function, consistent with dopamine stimulation stabilizing dopaminergic function. Loss of this autoregulation may contribute to dopaminergic dysfunction in brain disorders such as schizophrenia, substance dependence, and Parkinson's disease.

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