EFFECTS OF CGS-21680 IN-VIVO ON DOPAMINE D-2 AGONIST BINDING IN THE RAT-BRAIN

To investigate whether adenosine A(2a) agonists modulate dopamine D-2 receptor binding in vivo, we have analyzed the effects of intraperitoneally administered 2-[p-(carboxyethyl)phenylethylamino]-5'-N-ethylcarboxamidoadenosine (CGS 21680) on the ability of dopamine to compete at [I-125]iodosulpride (0.25 nM) binding sites in filter-wiped cryostat sections of the rat forebrain and on [H-3]L-(-)-N-propylnorapomorphine ([H-3]NPA) binding (1 nM) using quantitative receptor autoradiography. CGS 21680 (1-3 mg/kg) decreased the IC50 value of dopamine on [I-125]iodosulpride binding, and the decrease at 1 mg/kg was blocked by the A(2) antagonist 3,7-dimethyl-1-propargylxanthine (DMPX; 5 mg/kg). The decrease in the IC50 value of dopamine was due to a decrease in the K-L value whereas the K-H value and the proportion of high-affinity binding sites were unaffected. The binding of [H-3]NPA was significantly increased in the rostral and caudal parts of the caudate-putamen and in the rostral part of the olfactory tubercle, whereas no change could be demonstrated in the nucleus accumbens and in the caudal part of the olfactory tubercle. These results indicate that stimulation of A(2a) receptors in vivo causes alterations in the binding characteristics of D-2 receptors in certain regions of the basal ganglia.