Blockade of globus pallidus adenosine A 2A receptors displays antiparkinsonian activity in 6‐hydroxydopamine‐lesioned rats treated with D 1 or D 2 dopamine receptor agonists

We have recently demonstrated how antagonism of adenosine A 2A 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 A 2A receptor blockade on the motor stimulant effects elicited by dopamine receptor activation, hemiparkinsonian rats were infused with the water‐soluble A 2A antagonist SCH BT2 in the GP, alone or in combination with systemic administration of either SKF 38393 or quinpirole, to stimulate dopamine D 1 or D 2 receptors, respectively. SCH BT2 alone (5 μg/1 μl) 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 A 2A receptors exerts a facilitatory influence on the motor effects produced by the selective stimulation of either D 1 or D 2 dopamine receptors in hemiparkinsonian rats and suggest an involvement of GP in the antiparkinsonian activity of A 2A receptor antagonists. Synapse 62:345–351, 2008. © 2008 Wiley‐Liss, Inc.