Adenosine A2 receptors interact negatively with dopamine D1 and D2 receptors in unilaterally 6-hydroxydopamine-lesioned rats

Abstract

In rats bearing a unilateral 6-hydroxydopamine lesion of the dopaminergic nigro-striatal pathway, stimulation of adenosine A2 receptors by CGS 21680 reduced the contralateral turning behavior induced by L-3,4-dihydroxyphenylalanine (L-DOPA). Administration of CGS 21680 completely blocked the contralateral turning induced by the dopamine D1 receptor agonist, SKF 38393, and reduced the turning induced by the dopamine D2 receptor agonist, LY 171555. Quinolinic acid lesion of the striatum or 6-hydroxydopamine lesion of the dopaminergic nigro-striatal neurons demonstrated that [3H]CGS 21680 binding sites are associated to striatal intrinsic neurons. This study provides evidence for a negative postsynaptic interaction of both dopamine D1 and D2 receptors with adenosine A2 receptors.