Dopamine D1-like receptors play a key role in dopaminergic signaling.In addition to Gs/olf/adenylyl cyclase (AC)-coupled D1 receptors, the presence of D1-like receptors coupled to Gq/phospholipase C (PLC)has been proposed.By utilizing specific signaling inhibitors and biological agents in combination with the small interfering RNA (siRNA) approach, we investigated the D 1-like receptor signaling cascades, which modulated Gs/olf/adenylyl cyclase (AC)-coupled D 1 receptors agonist-induced cAMP-dependent protein kinase (PKA) activation at presynaptic sites.SKF83959 alone had no effects on the PKA activity, but could counteracted the D1 receptor agonist-induced PKA activation.