CCG-203920 potentiated NOP response in mouse striatal slices
Relying on the well-established NOP receptor inhibitory activity on D1 signaling (Olianas et al. , 2008), we next investigated whether RGS4 could affect the AT-403 mediated inhibition of the SKF-38393-induced ERK-positive cell number in slices of mouse striatum (Fig. 3). Application of the D1 receptor agonist SKF-38393 (100 μM) to striatal slices of naïve mice caused an approximately four-fold increase in the number of pERK immunoreactive cells over basal (three-way ANOVA, F1,42=213.909; Fig. 3). AT-403 alone (30 nM) had no effect on basal pERK levels but reduced D1 receptor-mediated response by 56% (three-way ANOVA, F1,42=102.746). CCG-203920, which was ineffective alone, significantly potentiated the effects of AT-403 (three-way ANOVA, F1,42=9.222). In fact, when co-applied with CCG-203920, AT-403 fully inhibited D1 stimulation.