The role of the globus pallidus D2 subfamily of dopamine receptors in pallidal immediate early gene expression

The globus pallidus plays an important role in basal ganglia circuitry, rep resenting the first relay nucleus of the 'indirect pathway' of striatal eff erents. In contrast to the well-characterized actions of dopamine on striat al neurons, the functional role of the dopamine innervation of globus palli dus is less well understood. Previous research showed that systemic adminis tration of either a dopamine D2 receptor antagonist or combined dopamine DI and D2 receptor agonists induces Fos, the protein product of the immediate early gene c-fos, in neurons of globus pallidus [Ruskin and Marshall (1997 ) Neuroscience 81, 79-92]. To determine whether the ability of the D2 recep tor antagonist, sulpiride, to induce Fos in rat pallidal neurons is mediate d by D2-like receptors in striatum or globus pallidus, intrastriatal or int rapallidal sulpiride infusions were conducted. The diffusion of intrastriat al sulpiride was estimated by measuring this antagonist's competition for N -ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ)-induced D2 receptor in activation. The phenotype of the striatal neurons expressing Fos after intr astriatal infusion was assessed by combining Fos immunocytochemistry with D 2 receptor mRNA in situ hybridization. Intrastriatal infusions of (-)-sulpi ride (10-200 ng) dose-dependently increased the number of striatal cells ex pressing Fos; and the Fos-immunoreactive striatal cells were D2 receptor mR NA-expressing, the same population in which systemic D2 receptor antagonist s induce Fos. Intrastriatal infusions of high (5 mug), but not low (10-200 ng), (-)-sulpiride doses also induced Fos in globus pallidus cells but the sulpiride appeared to spread to the globus pallidus. Direct intrapallidal i nfusions of (-)-sulpiride (50-100 ng) dose-dependently induced Fos in globu s pallidus with minimal influence on striatum or other basal ganglia struct ures. Using sensitive in situ hybridization conditions, prominent labeling of D2 receptor mRNA was evident in globus pallidus. D2 receptor mRNA was de nsest in a lateral 200 mum wide band that follows the curvature of the pall idal/striatal boundary. Cellular analysis revealed silver clusters associat ed with D2 receptor mRNA labeling over globus pallidus neurons that were im munoreactive for neuron-specific nuclear protein. These results strongly suggest that the dopaminergic innervation of globus pallidus, acting through D2-like receptors internal to this structure, can control gene expression in pallidal neurons. (C) 2001 IBRO. Published by El sevier Science Ltd. All rights reserved.