Stimulation of adenosine A1 receptors attenuates dopamine D1 receptor-mediated increase of NGFI-A, c-fos and jun-B mRNA levels in the dopamine-denervated striatum and dopamine D1 receptor-mediated turning behaviour

Adenosine A(1) receptors antagonistically and specifically modulate the binding and functional characteristics of dopamine D-1 receptors. In the striatum this interaction seems to take place in the GABAergic strionigro-strioentopeduncular 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 administration of psychostimulants and D-1 receptor agonists. Previous results suggest that a basal expression of the immediate-early gene c-fos tonically facilitates the functioning of strionigrostrioentopeduncular neurons and facilitates D-1 receptor-mediated motor activation. The role of A(1)receptors in the modulation of the expression of striatal D-1 receptor-regulated immediate-early genes and the D-1 receptor-mediated motor activation was investigated in rats with a unilateral lesion of the ascending dopaminergic pathways. The systemic administration of the A(1) agonist N-6-cyclopentyladenosine (CPA, 0.1 mg/kg) significantly decreased the number of contralateral turns 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 found that CPA (0.1 mg/kg) significantly inhibited the SKF 38393-induced increase in the expression of NGFI-A and c-fos mRNA levels in the dopamine-denervated striatum, The increase in jun-B mRNA expression could only be inhibited with the high dose of CPA (0.5 mg/kg), A stronger effect of the A(1) agonist was found in the ventral striatum (nucleus accumbens) compared with the dorsal striatum (dorsolateral caudate-putamen), The results indicate the existence of antagonistic A(1)-D-1 receptor-receptor interactions in the dopamine-denervated striatum controlling D-1 receptor transduction at supersensitive D-1 receptors.