THE FULL D-1 DOPAMINE-RECEPTOR AGONJST SKF-82958 INDUCES NEUROPEPTIDEMESSENGER-RNA IN THE NORMOSENSITIVE STRIATUM OF RATS - REGULATION OF D-1 D-2 INTERACTIONS BY MUSCARINIC RECEPTORS/

Neuropeptide and immediate early gene expression in striatonigral neur ons of the normosensitive striatum is induced by mixed D-1/D-2 recepto r agonists and indirect dopamine agonists, such as cocaine and ampheta mine. Both D-1 and D-2 receptor antagonists block these events. In con trast, the partial D-1 agonist, SKF-38393, does not evoke striatonigra l gene expression in intact rats. These findings have contributed to t he idea that both D-1 and D-2 receptors must be stimulated to evoke ge ne expression in striatonigral neurons. How these ''D-1/D-2 interactio ns'' are accomplished is unclear in light. of the controversy over whe ther striatonigral neurons express both D-1 and D-2 receptors. This st udy addresses these issues by demonstrating that in intact rats 1) a f ull D-1 receptor agonist, SKF-82958, induced behavioral activity and p reprodynorphin (PPD) and substance P (SP) gene expression in medium sp iny neurons in the dorsal, and especially, in the ventral striatum, 2) either a D-1 antagonist, SCH-23390, or a D-2 antagonist, eticlopride, blocked these effects, 3) the muscarinic antagonist, scopolamine, aug mented PPD and SP mRNA expression induced by SKF-82958 and prevented t he ability of eticlopride to block SKF-82958-induced PPD and SP mRNAs and 4) the SKF82958-induced increase in preproenkephalin mRNA in stria topallidal neurons was blocked by SCH-23390 or scopolamine but not by eticlopride. These data indicate that endogenous acetylcholine attenua tes D-1 receptor-stimulated PPD/SP gene expression in medium spiny neu rons, mediates D-1 receptor-stimulated preproenkephalin gene expressio n in striatopallidal neurons and contributes to D-2 receptor involveme nt in D-1-stimulated PPD/SP gene expression.