Vol. 281, Issue 2, 972-982, 1997

The Full D₁ Dopamine Receptor Agonist SKF-82958 Induces Neuropeptide mRNA in the Normosensitive Striatum of Rats: Regulation of D₁/D₂ Interactions by Muscarinic Receptors¹

John Q. Wang and Jacqueline F. McGinty

Department of Anatomy and Cell Biology, East Carolina University School of Medicine, Greenville, North Carolina

Neuropeptide and immediate early gene expression in striatonigral neurons of the normosensitive striatum is induced by mixed D₁/D₂ receptor agonists and indirect dopamine agonists, such as cocaine and amphetamine. Both D₁ and D₂ receptor antagonists block these events. In contrast, the partial D₁ agonist, SKF-38393, does not evoke striatonigral gene expression in intact rats. These findings have contributed to the idea that both D₁ and D₂ receptors must be stimulated to evoke gene expression in striatonigral neurons. How these "D₁/D₂ interactions" are accomplished is unclear in light of the controversy over whether striatonigral neurons express both D₁ and D₂ receptors. This study addresses these issues by demonstrating that in intact rats 1) a full D₁ receptor agonist, SKF-82958, induced behavioral activity and preprodynorphin (PPD) and substance P (SP) gene expression in medium spiny neurons in the dorsal, and especially, in the ventral striatum, 2) either a D₁ antagonist, SCH-23390, or a D₂ antagonist, eticlopride, blocked these effects, 3) the muscarinic antagonist, scopolamine, augmented PPD and SP mRNA expression induced by SKF-82958 and prevented the ability of eticlopride to block SKF-82958-induced PPD and SP mRNAs and 4) the SKF-82958-induced increase in preproenkephalin mRNA in striatopallidal neurons was blocked by SCH-23390 or scopolamine but not by eticlopride. These data indicate that endogenous acetylcholine attenuates D₁ receptor-stimulated PPD/SP gene expression in medium spiny neurons, mediates D₁ receptor-stimulated preproenkephalin gene expression in striatopallidal neurons and contributes to D₂ receptor involvement in D₁-stimulated PPD/SP gene expression.