2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane and Gambling

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

Topics: Adolescent; Adult; Aged; Anhedonia; Corpus Striatum; Decision Making; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Gambling; Humans; Impulsive Behavior; Male; Middle Aged; Psychometrics; Radiopharmaceuticals; Reward; Signal Transduction; Synapses; Tomography, Emission-Computed, Single-Photon; Tropanes; Young Adult

Repetitive Transcranial Magnetic Stimulation (rTMS) shows the potential to modulate local brain activity, thus resulting in a modulatory action on neurocircuitries implicated in the pathophysiology of Gambling Disorder (GD). We report the case of a GD patient treated with two weeks of high frequency (15 Hz) rTMS over the dorsolateral prefrontal cortex (DLPFC). At baseline and after rTMS treatment the patient underwent a SPECT examination with (123)I-FP-CIT tracer, to test changes in dopamine transporter (DAT) availability. The patient was followed up for six months, to explore safety and clinical correlates of a weekly high frequency rTMS maintenance treatment. Over the six-month follow-up the patient reported no episodes of gambling relapse. Also, the patient did not report craving for gambling or gambling-related symptoms. After two weeks of left DLPFC-rTMS treatment, we found a decrease in DAT availability in striatal regions, that represents a putative neurobiological substrate of dopaminergic pathways modulation. This study suggests that high frequency DLPFC-rTMS deserves further investigations in larger samples, using controlled study designs, to assess its real potential as a treatment for GD.

Topics: Adult; Caudate Nucleus; Craving; Dopamine Plasma Membrane Transport Proteins; Gambling; Humans; Male; Neostriatum; Prefrontal Cortex; Putamen; Recurrence; Tomography, Emission-Computed, Single-Photon; Transcranial Magnetic Stimulation; Tropanes

Pathological gambling (PG) represents a behavioral side effect of dopamine replacement therapy in a minority of patients with Parkinson's disease (PD). Using striatal dopamine transporter (DAT) with single photon emission tomography we assessed presynaptic dopaminergic function in 8 PD patients with PG, 21 matched PD control subjects, and 14 healthy subjects. Statistical Parametric Mapping was applied for image analysis. The analysis of variance (ANOVA) revealed that the three groups differed in dorsal and ventral striata bilaterally. The post-hoc analysis displayed a reduced tracer binding in the ventral striatum of PD patients with PG compared to PD controls, possibly reflecting either a reduction of mesolimbic projections or, alternatively, a lower membrane DAT expression on presynaptic terminals. The latter hypothesis is most likely given that the functional reduction of presynaptic reuptake would be more consistent with the increased dopamine levels in the ventral striatum recently reported in PD gamblers.

Topics: Aged; Basal Ganglia; Binding, Competitive; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Gambling; Humans; Male; Middle Aged; Neostriatum; Parkinson Disease; Protein Binding; Tomography, Emission-Computed, Single-Photon; Tropanes