title: In vivo evidence for greater amphetamine-induced dopamine release in pathological gambling: a positron emission tomography study with [(11)C]-(+)-PHNO.
abstract: Drug addiction has been associated with deficits in mesostriatal dopamine (DA) function, but whether this state extends to behavioral addictions such as pathological gambling (PG) is unclear. Here we used positron emission tomography and the D3 receptor-preferring radioligand [(11)C]-(+)-PHNO during a dual-scan protocol to investigate DA release in response to oral amphetamine in pathological gamblers (n=12) and healthy controls (n=11). In contrast with human neuroimaging findings in drug addiction, we report the first evidence that PG is associated with greater DA release in dorsal striatum (54-63% greater [(11)C]-(+)-PHNO displacement) than controls. Importantly, dopaminergic response to amphetamine in gamblers was positively predicted by D3 receptor levels (measured in substantia nigra), and related to gambling severity, allowing for construction of a mechanistic model that could help explain DA contributions to PG. Our results are consistent with a hyperdopaminergic state in PG, and support the hypothesis that dopaminergic sensitization involving D3-related mechanisms might contribute to the pathophysiology of behavioral addictions.
authors: 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] Addictions Program, Centre for Addiction and Mental Health, Toronto, ON, Canada [4] Schizophrenia Program, Centre for Addiction and Mental Health, Toronto, ON, Canada [5] Department of Psychiatry, University of Toronto, Toronto, ON, Canada [6] Campbell Family Mental Health Research Institute, Toronto, ON, Canada.
authors: I
authors: I
authors: Boileau
authors: 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, Toronto, ON, Canada.
authors: D
authors: D
authors: Payer
authors: Department of Pharmacology, University of Toronto, Toronto, ON, Canada.
authors: B
authors: B
authors: Chugani
authors: 1] Department of Psychiatry, University of Toronto, Toronto, ON, Canada [2] Campbell Family Mental Health Research Institute, Toronto, ON, Canada [3] Clinical Neuroscience Program, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors: D S S
authors: DS
authors: Lobo
authors: 1] Vivian M. Rakoff PET Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada [2] Campbell Family Mental Health Research Institute, Toronto, ON, Canada.
authors: S
authors: S
authors: Houle
authors: 1] Vivian M. Rakoff PET Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada [2] Campbell Family Mental Health Research Institute, Toronto, ON, Canada.
authors: A A
authors: AA
authors: Wilson
authors: 1] Department of Psychiatry, University of Toronto, Toronto, ON, Canada [2] Clinical Neuroscience Program, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors: J
authors: J
authors: Warsh
authors: 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, Toronto, ON, Canada [5] Department of Pharmacology, University of Toronto, Toronto, ON, Canada [6] Human Brain Laboratory, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors: S J
authors: SJ
authors: Kish
authors: 1] Campbell Family Mental Health Research Institute, Toronto, ON, Canada [2] Department of Pharmacology, University of Toronto, Toronto, ON, Canada [3] Clinical Neuroscience Program, Centre for Addiction and Mental Health, Toronto, ON, Canada [4] Department of Public Health Sciences, University of Toronto, Toronto, ON, Canada.
authors: M
authors: M
authors: Zack
mesh_terms: D000328:Adult; D000661:Amphetamine / Q000494:pharmacology*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D018491:Dopamine Agonists; D005715:Gambling / Q000000981:diagnostic imaging / Q000378:metabolism*; D006801:Humans; D008297:Male; D008959:Models, Neurological; D010078:Oxazines; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D050637:Receptors, Dopamine D3 / Q000378:metabolism; D012720:Severity of Illness Index
chemical_list: D015259:Dopamine Agents; D018491:Dopamine Agonists; D010078:Oxazines; D019275:Radiopharmaceuticals; D050637:Receptors, Dopamine D3; C042631:naxagolide; D000661:Amphetamine; D004298:Dopamine