Striatal presynaptic dopaminergic dysfunction in gambling disorder: A 123I‐FP‐CIT SPECT study

• Published in: Addiction biology Vol. 24; no. 5; pp. 1077 - 1086
• Main Authors: Pettorruso, Mauro, Martinotti, Giovanni, Cocciolillo, Fabrizio, De Risio, Luisa, Cinquino, Annarita, Di Nicola, Marco, Camardese, Giovanni, Migliara, Giuseppe, Moccia, Lorenzo, Conte, Eliana, Janiri, Luigi, Di Giuda, Daniela
• Format: Journal Article
• Language: English; Japanese
• Published: Leeds John Wiley & Sons, Inc 01.09.2019
• Subjects: Addictions; basal ganglia (putamen, caudate); behavioral addiction; Computed tomography; Decision making; Dopamine; Dopamine receptors; Dopamine transporter; dopamine transporter (DAT); Gambling; Hedonic response; Impulsive behavior; Iowa gambling task (IGT); Mental task performance; Neostriatum; neuroimaging; Putamen; Reinforcement; reward‐based decision making; Single photon emission computed tomography
• ISSN: 1355-6215; 1369-1600
• DOI: 10.1111/adb.12677

Although the involvement of dopamine in gambling disorder (GD) has long been hypothesized, its precise role remains unclear. The action of dopamine in the synapses is regulated by the dopamine transporter (DAT). We hereinafter present significant differences between a sample of 15 treatment‐seeking GD subjects and 17 healthy controls in terms of striatal DAT availability, and we explore its association with reward‐based decision making. We performed 123I‐FP‐CIT Single‐photon emission computed tomography (SPECT) and correlated DAT binding ratios in the bilateral caudate and putamen with gambling symptoms (G‐SAS, PG‐YBOCS) and behaviors, as well as other psychometric variables (anhedonia and impulsivity). Gambling disorder (GD) subjects were also administered a computerized version of the Iowa gambling task (IGT) to assess reward‐based decision making. We found reduced DAT availability in GD subjects compared with healthy controls (−13.30% in right caudate, −11.11% in right putamen, −11.44% in left caudate, and −11.46% in the left putamen). We also found that striatal DAT availability was inversely correlated with days spent gambling and IGT performance in GD subjects. These results provide evidence for a presynaptic dopaminergic dysfunction in striatal regions of GD subjects. Functional DAT down‐regulation possibly sustains the transition towards compulsive gambling addiction, characterized both by hyperdopaminergic and hypodopaminergic states in the context of a sensitized dopaminergic system. The action of dopamine in the synapses is regulated by the dopamine transporter (DAT). We found reduced DAT availability in the striatal regions of subjects with Gambling gambling Disorder disorder (i.e., −13.30% in right caudate compared to with healthy controls). Also, striatal DAT availability was inversely correlated with days spent gambling and Iowa Gambling gambling Task task performance. Functional DAT down‐regulation possibly sustains the transition towards compulsive gambling addiction, characterized both by hyperdopaminergic and hypodopaminergic states in the context of a sensitized dopaminergic system.