title: Imaging the D3 dopamine receptor across behavioral and drug addictions: Positron emission tomography studies with [(11)C]-(+)-PHNO.
abstract: Chronic drug use has been associated with dopaminergic abnormalities, detectable in humans with positron emission tomography (PET). Among these, a hallmark feature is low D2 dopamine receptor availability, which has been linked to clinical outcomes, but has not yet translated into a therapeutic strategy. The D3 dopamine receptor on the other hand has gained increasing attention, as, in contrast to D2, chronic exposure to drugs has been shown to up-regulate this receptor subtype in preclinical models of addiction-a phenomenon linked to dopamine system sensitization and drug-seeking. The present article summarizes the literature to date in humans, suggesting that the D3 receptor may indeed contribute to core features of addiction such as impulsiveness and cognitive impairment. A particularly useful tool in investigating this question is the PET imaging probe [(11)C]-(+)-PHNO, which binds to D2/3 dopamine receptors but has preferential affinity for D3. This technique has been used to demonstrate D3 up-regulation in humans, and can be applied to assess pharmacological interventions for development of D3-targeted strategies in addiction treatment.
authors.affiliation: Addiction Imaging Research Group, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada; Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada. Electronic address: isabelle.boileau@camh.ca.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Boileau
authors.affiliation: Multimodal Imaging Group & Geriatric Mental Health Division, Centre for Addiction and Mental Health, Toronto, ON, Canada; Keio University, School of Medicine, Department of Neuropsychiatry, Tokyo, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Nakajima
authors.affiliation: Addiction Imaging Research Group, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors.forename: Doris
authors.initials: D
authors.lastname: Payer
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006801:Humans; D010078:Oxazines; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D019966:Substance-Related Disorders / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000523:psychology
chemical_list: D010078:Oxazines; D019275:Radiopharmaceuticals; D050637:Receptors, Dopamine D3; C042631:naxagolide
keywords: Addiction; D(3) dopamine receptor; Impulsiveness; Positron emission tomography; [(11)C]-(+)-PHNO