Dopamine–Adenosine Interactions in the Striatum and the Globus Pallidus: Inhibition of Striatopallidal Neurons through Either D ₂ or A _2A Receptors Enhances D ₁Receptor-Mediated Effects on c-fos Expression

Abstract

D ₁ receptors located on striatonigral neurons and D ₂ receptors located, together with A _2Areceptors, on striatopallidal neurons are known to interact functionally. Using in situ hybridization, we examined the effects of D ₁ and D ₂ agonists and of an A _2A antagonist on c-fos mRNA in identified striatal neurons and in globus pallidus. The full D ₁agonist, SKF 82958 (1 mg/kg), induced a homogenous increase of c-fos mRNA in the striatum. This increase occurred to a similar extent in D ₁ and D ₂ receptor-containing striatal neurons. Conversely, the D ₂ agonist, quinelorane (2 mg/kg), decreased c-fos mRNA in these populations but increased it in globus pallidus. The adenosine A _2A receptor antagonist, SCH 58261 (5 mg/kg), also decreased c-fosmRNA in D ₂ receptor-containing neurons in striatum but did not affect pallidal c-fos mRNA. Concomitant administration of either D ₁ plus D ₂ agonists or D ₁ agonist plus A _2A antagonist caused a potentiation of c-fos mRNA in striatal neurons expressing the D ₁ receptor and in globus pallidus. However, only the combination of D ₁ and D ₂ agonists modified the c-fos mRNA expression to a “patchy” distribution. Our data show that (1) c-fos expression can be activated through D ₁ and inhibitedthrough A _2A or D ₂ receptors in both striatal output pathways in normal rats, and (2) D ₂ receptor stimulation as well as A _2A receptor blockade can interact with D ₁ 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 D ₁ and D ₂ agonists involves D ₂receptors located on interneurons or presynaptically on dopaminergic nerve terminals.