Abstract
As a behavioural addiction, gambling disorder (GD) provides an opportunity to characterize addictive processes without the potentially confounding effects of chronic excessive drug and alcohol exposure. Impulsivity is an established precursor to such addictive behaviours, and GD is associated with greater impulsivity. There is also evidence of GABAergic dysregulation in substance addiction and in impulsivity. This study therefore investigated GABAA receptor availability in 15 individuals with GD and 19 healthy volunteers (HV) using [11C]Ro15‐4513, a relatively selective α5 benzodiazepine receptor PET tracer and its relationship with impulsivity. We found significantly higher [11C]Ro15‐4513 total distribution volume (VT) in the right hippocampus in the GD group compared with HV. We found higher levels of the ‘Negative Urgency’ construct of impulsivity in GD, and these were positively associated with higher [11C]Ro15‐4513 VT in the amygdala in the GD group; no such significant correlations were evident in the HV group. These results contrast with reduced binding of GABAergic PET ligands described previously in alcohol and opiate addiction and add to growing evidence for distinctions in the neuropharmacology between substance and behavioural addictions. These results provide the first characterization of GABAA receptors in GD with [11C]Ro15‐4513 PET and show greater α5 receptor availability and positive correlations with trait impulsivity. This GABAergic dysregulation is potential target for treatment.
Highlights
There is considerable overlap between gambling disorder (GD) with drug and alcohol addiction with regard to clinical phenomenology and treatment, comorbidity, heritability and neurobiological profile (Clark 2014; Clark and Limbrick-Oldfield 2013)
In contrast to studies in cocaine and alcohol addiction, [11C]raclopride and [11C]-(+)-PHNO positron emission tomography (PET) revealed no differences in dopamine receptor DRD2/3 availability and greater stimulant-induced dopamine release in individuals with GD compared with healthy volunteers (HV; Albein-Urios et al 2012a,2012b; Boileau et al 2013; Boileau et al 2014)
As anxiety scores were significantly different in HV and individuals with GD (STAI; p = 0.001 and Spielberger State Anxiety Inventory (SSAI); p = 0.014) and anxiety is related to UPPS-P Negative Urgency (NU), we explored correlations between trait anxiety (STAI), state anxiety (SSAI), NU and [11C]Ro15-4513 VT in the 4 region of interest (ROI)
Summary
There is considerable overlap between gambling disorder (GD) (previously termed pathological gambling) with drug and alcohol addiction with regard to clinical phenomenology and treatment, comorbidity, heritability and neurobiological profile (Clark 2014; Clark and Limbrick-Oldfield 2013) Predicated on such evidence, this condition was recently reclassified from an ‘impulse control disorder’ in DSM-IV to the ‘substance-related. There is limited further evidence regarding the GABAergic system in individuals with GD, with some inconsistent evidence of greater GABA concentrations measured in the CSF in GD (Nordin and Sjodin 2007; Roy et al 1989) These observations, as well as the growing use of GABAergic medication such as baclofen and topiramate to treat addiction, indicate that it is timely and important to characterize the GABAA receptor system in GD (LingfordHughes et al 2012b). Based on the preclinical evidence, we hypothesized that impulsivity, the NU trait, in GD would be associated with higher [11C]Ro15-4513 binding; we have shown that [11C]Ro15-4513 is sensitive to GABA and low levels of GABA are associated with higher [11C]Ro15-4513 binding (Stokes et al 2014)
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