Abstract

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 D₂receptors 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 D₂receptors. 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 D₁antagonist, 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.