In the striatum, dopamine modulates these functions via cAMP/PKA signal-mediated mechanisms. Recent studies revealed that structural organization and cortical innervation are different among subregions of the striatum. Therefore, we investigated dopamine signaling in subregions of the striatum. Mouse striatal slices were divided into seven subregions: (1) rostral part, (2-1) intermediate medial part, (2-2) intermediate lateral part, (2-3) intermediate most lateral part, (3) caudal part, (4) most caudal part, (5) nucleus accumbens. Each slice was treated with a D1 receptor agonist, SKF81297 (1 μM) and activity of cAMP/PKA signal was evaluated with the phosphorylation of DARPP-32, GluA1. The stimulatory effects of SKF81297 on the phosphorylation were the lowest in the subregion (3) in the rostrocaudal axis and in the subregion (2-3) in the mediolateral axis. Treatment of slices with a PDE10A inhibitor, papaverine, or SKF81297 plus a muscarinic receptor antagonist, atropine, increased the phosphorylation in subregions where the effect of SKF81297 on the phosphorylation was low. Thus, dopamine D1 receptor/cAMP/PKA signaling is differentially regulated in each subregion of the striatum, and the differences are mediated by PDE10 and/or muscarinic receptor.