title: Dopamine and Opioid Neurotransmission in Behavioral Addictions: A Comparative PET Study in Pathological Gambling and Binge Eating.
abstract: Although behavioral addictions share many clinical features with drug addictions, they show strikingly large variation in their behavioral phenotypes (such as in uncontrollable gambling or eating). Neurotransmitter function in behavioral addictions is poorly understood, but has important implications in understanding its relationship with substance use disorders and underlying mechanisms of therapeutic efficacy. Here, we compare opioid and dopamine function between two behavioral addiction phenotypes: pathological gambling (PG) and binge eating disorder (BED). Thirty-nine participants (15 PG, 7 BED, and 17 controls) were scanned with [11C]carfentanil and [18F]fluorodopa positron emission tomography using a high-resolution scanner. Binding potentials relative to non-displaceable binding (BPND) for [11C]carfentanil and influx rate constant (Ki) values for [18F]fluorodopa were analyzed with region-of-interest and whole-brain voxel-by-voxel analyses. BED subjects showed widespread reductions in [11C]carfentanil BPNDin multiple subcortical and cortical brain regions and in striatal [18F]fluorodopa Kicompared with controls. In PG patients, [11C]carfentanil BPNDwas reduced in the anterior cingulate with no differences in [18F]fluorodopa Kicompared with controls. In the nucleus accumbens, a key region involved in reward processing, [11C]Carfentanil BPNDwas 30-34% lower and [18F]fluorodopa Kiwas 20% lower in BED compared with PG and controls (p<0.002). BED and PG are thus dissociable as a function of dopaminergic and opioidergic neurotransmission. Compared with PG, BED patients show widespread losses of mu-opioid receptor availability together with presynaptic dopaminergic defects. These findings highlight the heterogeneity underlying the subtypes of addiction and indicate differential mechanisms in the expression of pathological behaviors and responses to treatment.
authors.affiliation: Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland.|Department of Neurology, University of Turku, Turku, Finland.|Turku PET Centre, University of Turku, Turku, Finland.
authors.forename: Joonas
authors.initials: J
authors.lastname: Majuri
authors.affiliation: Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland.|Department of Neurology, University of Turku, Turku, Finland.|Turku PET Centre, University of Turku, Turku, Finland.
authors.forename: Juho
authors.initials: J
authors.lastname: Joutsa
authors.affiliation: Turku PET Centre, University of Turku, Turku, Finland.
authors.forename: Jarkko
authors.initials: J
authors.lastname: Johansson
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors.forename: Valerie
authors.initials: V
authors.lastname: Voon
authors.affiliation: Turku PET Centre, University of Turku, Turku, Finland.|Department of Radiology, University of Turku and Turku University Hospital, Turku, Finland.
authors.forename: Kati
authors.initials: K
authors.lastname: Alakurtti
authors.affiliation: Department of Radiology, University of Turku and Turku University Hospital, Turku, Finland.
authors.forename: Riitta
authors.initials: R
authors.lastname: Parkkola
authors.affiliation: Department of Health, Unit of Tobacco, Alcohol and Gambling, National Institute of Health and Welfare, Helsinki, Finland.
authors.forename: Tuuli
authors.initials: T
authors.lastname: Lahti
authors.affiliation: Department of Health, Unit of Tobacco, Alcohol and Gambling, National Institute of Health and Welfare, Helsinki, Finland.
authors.forename: Hannu
authors.initials: H
authors.lastname: Alho
authors.affiliation: Turku PET Centre, University of Turku, Turku, Finland.|Department of Radiology, University of Turku and Turku University Hospital, Turku, Finland.
authors.forename: Jussi
authors.initials: J
authors.lastname: Hirvonen
authors.affiliation: Turku PET Centre, University of Turku, Turku, Finland.|Turku PET Centre, Åbo Akademi University, Turku, Finland.
authors.forename: Eveliina
authors.initials: E
authors.lastname: Arponen
authors.affiliation: Turku PET Centre, University of Turku, Turku, Finland.|Turku PET Centre, Åbo Akademi University, Turku, Finland.
authors.forename: Sarita
authors.initials: S
authors.lastname: Forsback
authors.affiliation: Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland.|Department of Neurology, University of Turku, Turku, Finland.|Turku PET Centre, University of Turku, Turku, Finland.
authors.forename: Valtteri
authors.initials: V
authors.lastname: Kaasinen
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000378:metabolism*; D016739:Behavior, Addictive / Q000000981:diagnostic imaging / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002032:Bulimia / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D004295:Dihydroxyphenylalanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000031:analogs & derivatives; D005715:Gambling / Q000000981:diagnostic imaging / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals
chemical_list: D000701:Analgesics, Opioid; D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; C017114:carfentanil; D005283:Fentanyl; D004298:Dopamine