Effects of the JNK inhibitor SP600125 on the glutamate-stimulated JNK, ERK, and p38 activity and the DHPG-induced phosphorylation and expression of c-Jun in cultured rat striatal neurons. SP600125 concentration-dependently blocked the glutamate-stimulated JNK activity (A) but not ERK (B) or p38 (C) activity. Activity assays of the whole-cell fraction were conducted in striatal cultures treated with SP600125 (0.2, 1, or 5μm) incubated 15 min before and during a 10 min treatment with glutamate (50 μm). D, SP600125 blocked the DHPG-stimulated phosphorylation and expression of c-Jun without changing total levels of β-actin. SP600125 was incubated 15 min before and during a 1.5 h treatment with DHPG (100 μm). Western blots were probed with the antibody against phospho-c-Jun(Ser63), c-Jun, or β-actin. Representative immunoblots are shown to the left of the quantified data (mean ± SEM; n = 4–5). *p < 0.05 versus basal levels. +p < 0.05 versus glutamate or DHPG alone.