Increases in ERK, MSK1, and CREB phosphorylation after cocaine injection are suppressed in DKO mice. Immunodetection of pERKThr183/Tyr185, pMSK1Ser376, pMSK1Thr581, and pCREBSer133 in WT (Charles River Laboratories) and DKO mice. Images are three-dimensional reconstructions of optical z-stacks taken from the rostral, dorsomedial caudate–putamen. Arrows indicate neurons with nuclear pMSK1Ser376 immunolabeling. Scale bar, 80 μm. A significant interaction between treatment and genotype was found for all four phosphorylation events (one-way ANOVA, p < 0.0001; pairwise comparisons with Tukey's post hoc test: p < 0.05 between saline pERK groups, as well as between all cocaine groups; n = 4–5 mice per group). Dynph, Dynorphin.