ADENOSINE A(2) RECEPTORS STIMULATE C-FOS EXPRESSION IN STRIATAL NEURONS OF 6-HYDROXYDOPAMINE-LESIONED RATS

The induction of the early-gene c-fos after administration of the adenosine A(2a) receptor agonist CGS 21680, was studied in the striatum of normal rats or in rats with a unilateral B-hydroxydopamine lesion of the dopaminergic nigrostriatal neurons. CGS 21680 (2.5 mg/kg) induces c-Sos expression in the 6-hydroxydopamine-lesioned striatum, while up to 40 mg/kg fails to induce c-fos in the intact striatum or in the striatum of normal rats. Blockade of muscarinic receptors by scopolamine (5 mg/kg) partially prevents, and stimulation of dopamine D-2 receptors by quinpirole (0.5 mg/kg) completely reverses, CGS 21680-induced c-fos expression in the 6-hydroxydopamine-lesioned striatum. In turn, CGS 21680 partially reverses c-fos expression induced by quinpirole in the lesioned globus pallidus. CGS 21680, in addition, dose-dependently reduces the turning behavior induced by quinpirole (0.5 mg/kg) in 6-hydroxydopamine-lesioned rats. The results suggest that CGS 21680 induces c-fos expression in the striatum through direct and indirect mechanisms related to the ability of A(2a) receptors to stimulate cyclic AMP formation or acetylcholine release which in turn would activate c-fos through muscarinic receptors.