D1 receptors located on striatonigral neurons and D2 receptors located, together with A2A receptors, on striatopallidal neurons are known to interact functionally. Using in situ hybridization, we examined the effects of D1 and D2 agonists and of an A2A antagonist on c-fos mRNA in identified striatal neurons and in globus pallidus. The full D1 agonist, SKF 82958 (1 mg/kg), induced a homogenous increase of c-fos mRNA in the striatum. This increase occurred to a similar extent in D1 and D2 receptor-containing striatal neurons. Conversely, the D2 agonist, quinelorane (2 mg/kg), decreased c-fos mRNA in these populations but increased it in globus pallidus. The adenosine A2A receptor antagonist, SCH 58261 (5 mg/kg), also decreased c-fos mRNA in D2 receptor-containing neurons in striatum but did not affect pallidal c-fos mRNA. Concomitant administration of either D1 plus D2 agonists or D1 agonist plus A2A antagonist caused a potentiation of c-fos mRNA in striatal neurons expressing the D1 receptor and in globus pallidus. However, only the combination of D1 and D2 agonists modified the c-fos mRNA expression to a "patchy" distribution. Our data show that (1) c-fos expression can be activated through D1 and inhibited through A2A or D2 receptors in both striatal output pathways in normal rats, and (2) D2 receptor stimulation as well as A2A receptor blockade can interact with D1 receptor activation to potentiate c-fos expression in the striatum and the globus pallidus. The data also suggest that the topological alteration of c-fos expression after coadministration of D1 and D2 agonists involves D2 receptors located on interneurons or presynaptically on dopaminergic nerve terminals.