Pathological gambling: neurobiological bases and clinical aspects

The aim of this thesis was to investigate the 5-HTT and the A2A adenosine receptor affinity and density in platelet membranes of patients affected by PG, as compared with a group of healthy control subjects. In the first study seventeen PG patients were selected amongst those who were drug-free and at the first psychiatric interview in a Department of Addiction. The diagnosis was assessed according to DSM-IV criteria and PG severity was measured by means of the South Oaks Gambling Screen. The platelet [3H]-Par binding was carried out according to a standardized method. The binding parameters, the maximum binding capacity (Bmax) and the dissociation constant (Kd), were obtained by means of the Scatchard analysis. In the second study twelve drug-free PG patients and 12 healthy controls were enrolled in the study. The diagnosis was assessed according to Structured Clinical Interview for DSM-IV-Patient Version 2.0 and the South Oaks Gambling Screen. A2A adenosine receptor binding parameters were evaluated using [3H]ZM241385 binding assay: affinity (Kd) and density (Bmax) were obtained by the means of saturation binding studies on platelet membranes. As far as the results of the first study are concerned, the Bmax values of PG patients were significantly lower than that of healthy subjects, while the Kd values were not different in the two groups. No significant effect of age, sex or psychiatric comorbidity on Bmax or Kd was observed; there were also no correlations between clinical and biological variables. In the second study, the A2A adenosine receptor affinity resulted as significant higher in patients affected by PG, with respect to healthy subjects; on the other hand, no significant changes in the Bmax value were evidenced between the two groups. In conclusion, PG patients showed a dysfunction at the level of the platelet SERT that would suggest the involvement of the 5-HT system in this condition. The increase in A2A adenosine receptor binding affinity in PG patients with respect to control subjects demonstrate, for the first time, the involvement of the adenosine system in this pathology. These data open the way to new therapeutical approaches for the treatment of pathological gambling.