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The D2/3 dopamine receptor in pathological gambling: a positron emission tomography study with [11C]-(+)-propyl-hexahydro-naphtho-oxazin and [11C]raclopride

Authors

  • Isabelle Boileau,

    Corresponding author
    1. Vivian M. Rakoff PET Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
    2. Addictions Program, Centre for Addiction and Mental Health, Toronto, ON, Canada
    3. Schizophrenia Program, Centre for Addiction and Mental Health, Toronto, ON, Canada
    4. Department of Psychiatry, University of Toronto, Toronto, ON, Canada
    5. Campbell Family Mental Health Research Institute
    • Addiction Imaging Research Group, Centre for Addiction and Mental Health, Toronto, ON, Canada
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  • Doris Payer,

    1. Addiction Imaging Research Group, Centre for Addiction and Mental Health, Toronto, ON, Canada
    2. Vivian M. Rakoff PET Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
    3. Department of Psychiatry, University of Toronto, Toronto, ON, Canada
    4. Campbell Family Mental Health Research Institute
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  • Bindiya Chugani,

    1. Department of Pharmacology, University of Toronto, Toronto, ON, Canada
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  • Daniela Lobo,

    1. Clinical Neuroscience Program, Centre for Addiction and Mental Health, Toronto, ON, Canada
    2. Department of Psychiatry, University of Toronto, Toronto, ON, Canada
    3. Department of Pharmacology, University of Toronto, Toronto, ON, Canada
    4. Campbell Family Mental Health Research Institute
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  • Arian Behzadi,

    1. Addiction Imaging Research Group, Centre for Addiction and Mental Health, Toronto, ON, Canada
    2. Vivian M. Rakoff PET Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
    3. Department of Psychiatry, University of Toronto, Toronto, ON, Canada
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  • Pablo M. Rusjan,

    1. Vivian M. Rakoff PET Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
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  • Sylvain Houle,

    1. Vivian M. Rakoff PET Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
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  • Alan A. Wilson,

    1. Vivian M. Rakoff PET Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
    2. Campbell Family Mental Health Research Institute
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  • Jerry Warsh,

    1. Clinical Neuroscience Program, Centre for Addiction and Mental Health, Toronto, ON, Canada
    2. Department of Psychiatry, University of Toronto, Toronto, ON, Canada
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  • Stephen J. Kish,

    1. Addiction Imaging Research Group, Centre for Addiction and Mental Health, Toronto, ON, Canada
    2. Vivian M. Rakoff PET Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
    3. Human Brain Laboratory, Centre for Addiction and Mental Health, Toronto, ON, Canada
    4. Department of Psychiatry, University of Toronto, Toronto, ON, Canada
    5. Department of Pharmacology, University of Toronto, Toronto, ON, Canada
    6. Campbell Family Mental Health Research Institute
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  • Martin Zack

    1. Clinical Neuroscience Program, Centre for Addiction and Mental Health, Toronto, ON, Canada
    2. Department of Pharmacology, University of Toronto, Toronto, ON, Canada
    3. Department of Public Health Sciences, University of Toronto, Toronto, ON, Canada
    4. Campbell Family Mental Health Research Institute
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Correspondence to: Isabelle Boileau, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, Canada M5T 1R8. E-mail: isabelle_boileau@camh.net

Abstract

Aims

Pathological gambling (PG) shares diagnostic features with substance use disorder (SUD), but the neurochemical mechanisms underlying PG are poorly understood. Because dopamine (DA), a neurotransmitter implicated in reward and reinforcement, is probably involved, we used positron emission tomography (PET) to test whether PG is associated with abnormalities in D2 and D3 receptor levels, as observed in SUD.

Design

Case–control study comparing PG to healthy control (HC) subjects.

Setting

Academic research imaging centre.

Participants

Thirteen non-treatment-seeking males meeting DSM-IV criteria for PG, and 12 matched HC (11 of whom completed PET).

Measurements

Two PET scans (one with the D3 receptor preferring agonist [11C]-(+)-propyl-hexahydro-naphtho-oxazin (PHNO) and the other with [11C]raclopride) to assess D2/3 DA receptor availability, and behavioural measures (self-report questionnaires and slot-machine game) to assess subjective effects and relationships to PET measures.

Findings

Binding of both radiotracers did not differ between groups in striatum or substantia nigra (SN) (all P > 0.1). Across PG, [11C]-(+)-PHNO binding in SN, where the signal is attributable primarily to D3 receptors, correlated with gambling severity (r = 0.57, P = 0.04) and impulsiveness (r = 0.65, P = 0.03). In HC, [11C]raclopride binding in dorsal striatum correlated inversely with subjective effects of gambling (r = −0.70, P = 0.03) and impulsiveness (r = −0.70, P = 0.03).

Conclusions

Unlike with substance use disorder, there appear to be no marked differences in D2/D3 levels between healthy subjects and pathological gamblers, suggesting that low receptor availability may not be a necessary feature of addiction. However, relationships between [11C]-(+)-PHNO binding and gambling severity/impulsiveness suggests involvement of the D3 receptor in impulsive/compulsive behaviours.

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