KOR activation produces p38 MAPK phosphorylation in males and females, but not ERK 1/2 phosphorylation in females. A, Striatal mRNA from male and female mice was isolated and analyzed for KOR expression by qRT-PCR. No difference in KOR expression was observed (n = 8 per group) (B,C). Mice were injected with U50488 (10 mg/kg, i.p.) or saline 15 or 30 min before isolating striatal proteins. Phosphorylation of p38 (B) and ERK1/2 phosphorylation (C) in ventral striatum of male and female mice by Western blot analysis is shown. B, U50488 induced p38 phosphorylation in male and female mice. There was a significant effect of U50488 (p < 0.001), with no difference between males (n = 11) and females (n = 8). C, U50488 induced ERK1/2 phosphorylation (p < 0.001) in male (n = 5–6) but not female (n = 8) mice and males were significantly different from females (p < 0.001). D, Representative blots for B. E, Representative blots for C. F, Representative blots for G and H. G, U50488 induced p38 phosphorylation in male and female mice (n = 7–9 per group) in spinal cord homogenates (bracket indicates main effect of treatment; p < 0.05). H, U50488 induced ERK phosphorylation in male (n = 7–9 per group) but not female (n = 9 per group) mice (p < 0.05). Error bars indicate SEM.*p < 0.05, **p < 0.01, ***p < 0.001, n.s., not significant.