Abstract
Background/Aims: A structural and functional interaction between A<sub>2A</sub> adenosine receptors and D<sub>2</sub> dopamine receptors has been implicated in the pathophysiology of impulse control disorders. The aim of this study was to use platelet membranes to assess A<sub>2A</sub> adenosine receptor affinity and density in patients affected by pathological gambling (PG; which is classified as a specific impulse control disorder) with respect to those of control subjects. Methods: Twelve drug-free PG patients and 12 age- and sex-matched healthy controls were enrolled in the study. PG was diagnosed according to the Structured Clinical Interview for DSM-IV – Patient Version 2.0 and the South Oaks Gambling Screen. A<sub>2A</sub> adenosine receptor binding parameters were evaluated using a [<sup>3</sup>H]ZM<sub>241385</sub> binding assay; affinity and density (B<sub>max</sub>) were determined by means of saturation binding studies with platelet membranes. Results: The A<sub>2A</sub> adenosine receptor binding affinity was found to be significantly higher in patients affected by PG than in healthy subjects; in contrast, no significant differences in B<sub>max</sub> were observed between the 2 groups. Conclusions: The elevated A<sub>2A</sub> adenosine receptor binding affinity in platelets from PG patients with respect to control subjects demonstrates for the first time a change in adenosine receptor parameters, and it suggests the involvement of the adenosine system in this pathology. The previously demonstrated hyperactivity of the dopamine system in PG may modulate the A<sub>2A</sub> adenosine receptor, supporting a role for this receptor as a peripheral marker of dopamine dysfunction. Because it is not possible to directly measure the D<sub>2</sub> dopamine receptor in human platelets, these data are particularly relevant to the detection of dopamine dysfunction.
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