Dopamine–Adenosine Interactions in the Striatum and the Globus Pallidus: Inhibition of Striatopallidal Neurons through Either D2 or A2A Receptors Enhances D1Receptor-Mediated Effects on c-fos Expression

摘要

D1 receptors located on striatonigral neurons and D2 receptors located, together with A2Areceptors, 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 D1agonist, SKF 82958 (1 mg/kg), induced a homogenous increase ofc-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-fosmRNA 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 inhibitedthrough A_2A or D₂ receptors in both striatal output pathways in normal rats, and (2) D₂ receptor stimulation as well as A_2A receptor blockade can interact with D₁ receptor activation to potentiatec-fos expression in the striatum and the globus pallidus. The data also suggest that the topological alteration ofc-fos expression after coadministration of D₁ and D₂ agonists involves D₂receptors located on interneurons or presynaptically on dopaminergic nerve terminals.