Blockade of A2a adenosine receptors positively modulates turning behaviour and c-Fos expression induced by D1 agonists in dopamine-denervated rats.

In rats with unilateral 6-hydroxydopamine lesions of the dopaminergic nigrostriatal pathway, administration of the A2a adenosine antagonist SCH 58261 alone did not induce any motor asymmetry but strongly potentiated the contralateral turning behaviour induced by the dopamine D1 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 D1-dependent turning behaviour and c-Fos expression was also observed after administration of the A2a/A1 antagonist CGS 15943. Administration of the A1 adenosine receptor antagonist DPCPX induced a small potentiation of D1-mediated contralateral turning while c-Fos expression induced by SKF 38393 was not modified. The results suggest that endogenous adenosine acting on A2a receptors can exert an inhibitory influence on the functional expression of D1-mediated responses in dopamine-denervated rats, and propose new possible therapeutic approaches in the treatment of Parkinson's disease.