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Volume 17, Number 20, Issue of October 15, 1997 pp. 8038-8048
Copyright ©1997 Society for Neuroscience

Dopamine-Adenosine Interactions in the Striatum and the Globus Pallidus: Inhibition of Striatopallidal Neurons through Either D₂ or A_2A Receptors Enhances D₁ Receptor-Mediated Effects on c-fos Expression

Received May 19, 1997; revised July 21, 1997; accepted Aug. 5, 1997.

Catherine Le Moine¹, Per Svenningsson², Bertil B. Fredholm², and Bertrand Bloch¹

¹ Centre National de la Recherche Scientifique Unité Mixte de Recherche 5541, Laboratoire d'Histologie Embryologie, Institut Federatif de Recherche de Neurosciences Cliniques et Expérimentales, Université de Bordeaux II, 33076 Bordeaux Cedex, France, and ² Section of Molecular Neuropharmacology, Department of Physiology and Pharmacology, Karolinska Institutet, S-17177 Stockholm, Sweden

D₁ receptors located on striatonigral neurons and D₂ receptors located, together with A_2A 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 A_2A 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 A_2A 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 A_2A 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 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 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.

Key words: In situ hybridization; phenotypical characterization; immediate early gene; dopamine-adenosine interactions; synergistic effects; striatal output pathways; globus pallidus

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