Increasing cGMP production reduces D1R agonist-induced cAMP levels and GluA1 surface expression by activating PDE2. Data are represented as mean ± S.E. normalized to baseline. A, SNAP significantly increases cGMP levels. 0.1 μm A68930 was added after 5 min of baseline, followed by DMSO (gray, eight cells) or 50 μm SNAP (black, eight cells). ***, p = 0.0001 (repeated measures two-way ANOVA, F1,19 = 27.00). B, increasing cGMP production decreases D1R agonist-induced cAMP levels via modulation of PDE2. After 5 min of baseline, 0.1 μm A68930 was added for 10 min, followed by DMSO (replotted from Fig. 1 for comparison) or 50 μm SNAP (black, 21 cells) or 1.0 μm BAY60-7550 + 50 μm SNAP (black open square, seven cells). ***, p = 0.0009 (repeated measures two-way ANOVA, DMSO versus SNAP, F1,36 = 25.84); p < 0.0001 (repeated measures two-way ANOVA, SNAP versus SNAP + BAY60-7550, F1,26 = 74.03). C, increasing cGMP reduces GluA1 surface expression by activating PDE2. After 5 min of baseline, the D1R agonist A68930 (0.1 μm) was added for 10 min, followed by DMSO (replotted from Fig. 1 for comparison) or 50 μm SNAP (black squares, 11 cells) or 1.0 μm BAY60-7550 + 50 μm SNAP (black open squares, 10 cells). ***, p < 0.0001 (repeated measures two-way ANOVA, DMSO versus SNAP, F1,36 = 26.31). **, p = 0.0061 (two-way ANOVA, SNAP versus BAY60-7550 + SNAP, F1,19 = 9.50). D, SNAP alone has no effect on GluA1 surface insertion. 50 μm SNAP was added after 5 min of baseline (six cells).