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 intraperiton eally administered l)phenylethylamino]-5'-N-ethylcarboxamidoadenosine (CGS 21680) on the ability of dopamine to compete at [I-125]iodosulpri de (0.25 nM) binding sites in filter-wiped cryostat sections of the ra t forebrain and on [H-3]L-(-)-N-propylnorapomorphine ([H-3]NPA) bindin g (1 nM) using quantitative receptor autoradiography. CGS 21680 (1-3 m g/kg) decreased the IC50 value of dopamine on [I-125]iodosulpride bind ing, 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 IC 50 value of dopamine was due to a decrease in the K-L value whereas th e K-H value and the proportion of high-affinity binding sites were una ffected. The binding of [H-3]NPA was significantly increased in the ro stral 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 c auses alterations in the binding characteristics of D-2 receptors in c ertain regions of the basal ganglia.