Blockade of A(2a) adenosine receptors positively modulates turning behaviour and c-Fos expression induced by D-1 agonists in dopamine-denervated rats

In rats with unilateral 6-hydroxydopamine lesions of the dopaminergic nigrostriatal pathway, administration of the A(2a) adenosine antagonist SCH 58261 alone did not induce any motor asymmetry but strongly potentiated the contralateral turning behaviour induced by the dopamine D-1 agonist SKF 38393. SCH 58261 also increased the number of Fos-like positive nuclei induced by SKF 38393 in the 6-hydroxydopamine-lesioned striatum. intense potentiation of D-1-dependent turning behaviour and c-Fos expression was also observed after administration of the A(2a)/A(1) antagonist CGS 15943. Administration of the A(1) adenosine receptor antagonist DPCPX induced a small potentiation of D-1-mediated contralateral turning while c-Fos expression induced by SKF 38393 was not modified. The results suggest that endogenous adenosine acting on A(2a) receptors can exert an inhibitory influence on the functional expression of D-1-mediated responses in dopamine-denervated rats, and propose new possible therapeutic approaches in the treatment of Parkinson's disease.