Increases in Striatal Acetylcholine by SKF-38393 Are Mediated Through D1 Dopamine Receptors in Striatum and Not the Frontal Cortex

It has been proposed by some that the D1 receptor effects are mediated through striatal actions while others have suggested that they are determined indirectly through the frontal cortex. The experiments reported here represent a further attempt to resolve this controversy. It was found that focal applications of the inactive and active enantiomers of SKF-38393 (a D1 dopamine receptor agonist) to the rat striatum via reverse dialysis increased extracellular acetylcholine (ACh) in a stereoselective manner. Infusions of SKF-38393 into the frontal cortex, on the other hand, were ineffective in altering striatal ACh. Furthermore, partial hemisections caudal to the frontal cortex did not alter the ability of systemically administrated SKF-38393 to increase striatal ACh. Taken together, these results suggest that at least some of the effects of D1 receptor agonists on striatal cholinergic function are mediated through actions in the striatum and not the frontal cortex.