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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

1999; Wiley; Volume: 11; Issue: 11 Linguagem: Inglês

10.1046/j.1460-9568.1999.00810.x

1460-9568

Sergi Ferré, Roberto Rimondini, Patrizia Popoli, Rosaria Reggio, Antonella Pèzzola, Anita C. Hansson, Annica Andersson, Kjell Fuxé,

Receptor Mechanisms and Signaling

Abstract 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 strionigro‐strioentopeduncular 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.