Impact of an Adenosine A Receptor Agonist and Antagonist on Binding of the Dopamine D Receptor Ligand [C]raclopride in the Rodent Striatum.

Adenosine A and dopamine D receptors in the basal ganglia form heterotetrameric structures that are involved in the regulation of motor activity and neuropsychiatric functions. The present study examines the A receptor-mediated modulation of D receptor binding in vivo using positron emission tomography (PET) with the D antagonist tracer [C]raclopride. Healthy male Wistar rats ( = 8) were scanned (60 min dynamic scan) with [C]raclopride at baseline and 7 days later following an acute administration of the A agonist CGS21680 (1 mg/kg), using a MicroPET Focus-220 camera. Nondisplaceable binding potential (BP) values were calculated using a simplified reference tissue model (SRTM), with cerebellum as the reference tissue. SRTM analysis did not show any significant changes in [C]raclopride BP ( = 0.102) in striatum after CGS21680 administration compared to the baseline. As CGS21680 strongly affects hemodynamics, we also used arterial blood sampling and a metabolite-corrected plasma input function for compartment modeling using the reversible two-tissue compartment model (2TCM) to obtain the BP from the / ratio and from the striatum/cerebellum volume of distribution ratio (DVR) in a second group of animals. These rats underwent dynamic [C]raclopride scans after pretreatment with a vehicle ( = 5), a single dose of CGS21680 (1 mg/kg, = 5), or a single dose of the A antagonist KW6002 (1 mg/kg, = 5). The parent fraction in plasma was significantly higher in the CGS21680-treated group ( = 0.0001) compared to the vehicle-treated group. GCS21680 administration significantly reduced the striatal / ratio ( < 0.01), but and estimates may be less reliable. The BP (DVR-1) decreased from 1.963 ± 0.27 in the vehicle-treated group to 1.53 ± 0.55 ( = 0.080) or 1.961 ± 0.11 ( = 0.993) after the administration of CGS21680 or KW6002, respectively. Our study suggests that the A agonist CGS21680, but not the antagonist KW6002, may reduce the D receptor availability in the striatum.