Figure 5.
rpS6 Activation by ERK in Hdc-KO mice. (A) Phospho-S235/236 rpS6, which is regulated by MAPK, was elevated in the dorsal striatum in Hdc-KO mice and after amphetamine, as measured by immunohistochemistry and cell counting by an observer blind to genotype and condition (2-way ANOVA: main effect of genotype: F[1,4]=19.93; p=0.01; main effect of amphetamine: F [1,4]=39.20; p=0.004). (B) Elevated pS235/236-rpS6 was attenuated by systemic administration of the MAPK kinase inhibitor SL-327, as assayed by immunohistochemistry and cell counting (main effect of genotype: F[1,4]=79.07, p=0.001; main effect of SL-327: F[1,4]=222.9, p=0.0001; genotype × SL-327 interaction: F[1,4]=8.557, p=0.04). (C) Elevated pS235/236-rpS6 in Hdc-KO mice and after amphetamine was corroborated by Western blotting of striatal extracts (2-way ANOVA: main effect of genotype: F[1,14] =16.78; p=0.0008; main effect of amphetamine: F[1,41]=54.42; p<0.0001; genotype × amphetamine interaction: F[1,14]=12.64; p=0.003).