In vivo evidence for greater amphetamine-induced dopamine release in pathological gambling: a positron emission tomography study with [11C]-(+)-PHNO

• Published in: Molecular psychiatry Vol. 19; no. 12; pp. 1305 - 1313
• Main Authors: Boileau, I, Payer, D, Chugani, B, Lobo, D S S, Houle, S, Wilson, A A, Warsh, J, Kish, S J, Zack, M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2014; Nature Publishing Group
• Subjects: 631/378/548/1964; 631/92/436; 692/699/476/5; Addictions; Addictive behaviors; Adult; Adult and adolescent clinical studies; Amphetamine - pharmacology; Amphetamines; Behavioral Sciences; Biological and medical sciences; Biological Psychology; Brain - diagnostic imaging; Brain - drug effects; Brain - metabolism; Caudate-putamen; Cocaine; Dopamine; Dopamine - metabolism; Dopamine Agents - pharmacology; Dopamine Agonists; Dopamine D3 receptors; Drug addiction; Drug use; Gambling; Gambling - diagnostic imaging; Gambling - metabolism; Health care; Humans; Hypotheses; Male; Medical imaging; Medical research; Medical sciences; Medicine; Medicine & Public Health; Mental disorders; Mental health; Miscellaneous; Models, Neurological; Neostriatum; Neuroimaging; Neuropharmacology; Neurosciences; original-article; Oxazines; Parkinson's disease; Pharmacology. Drug treatments; Pharmacotherapy; Positron emission tomography; Psychiatry; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Radiopharmaceuticals; Receptors, Dopamine D3 - metabolism; Severity of Illness Index; Social behavior disorders. Criminal behavior. Delinquency; Substance use disorder; Substantia nigra; Tomography; Canada; C]-(+)-PHNO; pathological gambling; amphetamine; [; sensitization; positron emission tomography; dopamine; Amphetamine derivatives; Radionuclide study; Impulse control disorder; Dopamine; CNS stimulant; Psychotropic; Catecholamine; Pathological gambling; Neurotransmitter; Amfetamine; Sensitization; Positron emission tomography; Release; Emission tomography
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/mp.2013.163

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 D 3 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 D 3 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 D 3 -related mechanisms might contribute to the pathophysiology of behavioral addictions.