A2A adenosine receptor binding parameters in platelets from patients affected by pathological gambling

BACKGROUND/AIMS: A structural and functional interaction between A(2A) adenosine receptors and D(2) 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(2A) 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(2A) adenosine receptor binding parameters were evaluated using a [(3)H]ZM(241385) binding assay; affinity and density (B(max)) were determined by means of saturation binding studies with platelet membranes. RESULTS: The A(2A) 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(max) were observed between the 2 groups. CONCLUSIONS: The elevated A(2A) 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(2A) 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(2) dopamine receptor in human platelets, these data are particularly relevant to the detection of dopamine dysfunction.