Stimulation of adenosine A(1) receptors attenuates dopamine D-1 receptor-mediated increase of NGFI-A, c-fos and jun-B mRNA levels in the dopamine-denervated striatum and dopamine D-1 receptor-mediated turning behaviour

Adenosine A(1) receptors antagonistically and specifically modulate the bin ding and functional characteristics of dopamine D-1 receptors. In the stria tum this interaction seems to take place in the GABAergic strionigro-strioe ntopeduncular neurons, where both receptors are colocalized. D-1 receptors in the strionigro-strioentopeduncular neurons are involved in the increased striatal expression of immediate-early genes induced by the systemic admin istration of psychostimulants and D-1 receptor agonists. Previous results s uggest that a basal expression of the immediate-early gene c-fos tonically facilitates the functioning of strionigrostrioentopeduncular neurons and fa cilitates D-1 receptor-mediated motor activation. The role of A(1)receptors in the modulation of the expression of striatal D-1 receptor-regulated imm ediate-early genes and the D-1 receptor-mediated motor activation was inves tigated in rats with a unilateral lesion of the ascending dopaminergic path ways. The systemic administration of the A(1) agonist N-6-cyclopentyladenos ine (CPA, 0.1 mg/kg) significantly decreased the number of contralateral tu rns induced by the D-1 agonist SKF 38393 (3 mg/kg). Higher doses of CPA (0. 5 mg/kg) were necessary to inhibit the turning behaviour induced by the D-2 agonist quinpirole (0.1 mg/kg). By using in situ hybridization it was foun d that CPA (0.1 mg/kg) significantly inhibited the SKF 38393-induced increa se in the expression of NGFI-A and c-fos mRNA levels in the dopamine-denerv ated striatum, The increase in jun-B mRNA expression could only be inhibite d with the high dose of CPA (0.5 mg/kg), A stronger effect of the A(1) agon ist was found in the ventral striatum (nucleus accumbens) compared with the dorsal striatum (dorsolateral caudate-putamen), The results indicate the e xistence of antagonistic A(1)-D-1 receptor-receptor interactions in the dop amine-denervated striatum controlling D-1 receptor transduction at supersen sitive D-1 receptors.