Blockade of globus pallidus adenosine A2A receptors displays antiparkinsonian activity in 6-hydroxydopamine-lesioned rats treated with D 1 or D2 dopamine receptor agonists

We have recently demonstrated how antagonism of adenosine A2A receptors within the globus pallidus (GP) ipsilateral to dopaminergic denervation potentiates contralateral rotational behavior induced by the dopamine precursor L-DOPA in 6-hydroxydopamine-lesioned hemiparkinsonian rats. To further characterize the influence of pallidal A2A receptor blockade on the motor stimulant effects elicited by dopamine receptor activation, hemiparkinsonian rats were infused with the water-sol. A2A antagonist SCH BT2 in the GP, alone or in combination with systemic administration of either SKF 38393 or quinpirole, to stimulate dopamine D1 or D2 receptors, resp. SCH BT2 alone (5 g/1 l) neither altered motor behavior nor produced postural asymmetry. In contrast, the contralateral rotations elicited by SKF 38393 (1.5 mg/kg) as well as quinpirole (0.05 mg/kg) were potentiated by the concomitant intrapallidal infusion of SCH BT2. The results of this study demonstrate that blockade of pallidal A2A receptors exerts a facilitatory influence on the motor effects produced by the selective stimulation of either D1 or D2 dopamine receptors in hemiparkinsonian rats and suggest an involvement of GP in the antiparkinsonian activity of A2A receptor antagonists.