relationship between dopamine agonist stimulation of inositol phosphate formation and cytidine diphosphatediacylglycerol accumulation in brain slices dopamine receptorcoupled stimulation of inositol phosphate formation has been characterized extensively but little is known about the diacylglycerol arm of this dualsignaling pathway this study examined several parameters of cytidine diphosphatediacylglycerol cdpdg accumulation as an index of agoniststimulated dg formation rat brain slices prelabeled with 53hcytidine were incubated with various test agents in the presence of licl and accumulated cdpdg analyzed dopamine and skf38393 significantly and dosedependently stimulated cdpdg accumulation skf38393 responses were inhibited by neomycin and reversed by myoinositol or by exclusion of licl compared to inositol phosphate formation in 23hinositolprelabeled slices the cdpdg responses were proportionately greater while the agonist ec50 values were similar between the two assays the d1receptor antagonist sch23390 inhibited skf38393mediated responses at 0110 microm concentrations whereas greater concentrations reversed the inhibition skf38393 effects were completely blocked by the dg kinase inhibitor r59022 thus precluding any role for phospholipased or de novo phosphatidate synthesis in the dopaminergic response d609 which inhibits phosphatidylcholinespecific phospholipasec plc potently inhibited both cdpdg accumulation and inositol phosphate formation these findings demonstrate that the selective d1receptor antagonist sch23390 is a partial agonist at the d1like dopamine receptor that couples to phosphoinositide signaling that dopaminergic facilitation of phosphoinositide signaling is independent of de novo phosphatidate synthesis and that the widely used enzyme inhibitor d609 is probably not selective for phosphatidylcholinespecific plc in brain slice preparations the greater sensitivity of the cdpdg measurement presents this assay as a reliable and possibly superior index of dopamine receptorcoupled plc activation in intact tissues