Fig. 3

SP600125 delays tolerance for the antinociceptive effects of chronically administered morphine. Chronic tolerance to the antinociceptive effects of morphine is mediated by JNK signaling. Wild-type mice were treated with vehicle (black line with triangles), 3 mg/kg SP600125 (SP6; dashed black line with diamonds), or 10 mg/kg SP600125 (SP6; black line with diamonds) 60 min prior to administration of 10 mg/kg morphine for ten consecutive days. Treatment with either 3 mg/kg or 10 mg/kg SP600125 delayed tolerance to the effects of chronically administered morphine in the tail-flick test and the hot plate test. Treatment with either 3 mg/kg or 10 mg/kg SP600125 also reduced tolerance for the hypothermic effects of chronically administered morphine. Tail-flick antinociception (a), hotplate antinociception (b), and body temperature (c) were measured 60 min later. Acute treatment with SP600125 alone (3 mg/kg or 10 mg/kg) had no effect on tail-flick antinociception (p = 0.79), hotplate antinociception (p = 0.36), or hypothermia (p = 0.5) (d). Data are expressed as mean ± S.E.M. (n = 9–19 per group). *p < 0.007 for SP600125 (3 or 10 mg/kg) vs. vehicle group (ANOVA, Bonferroni post hoc); + p < 0.003 for SP600125 (3 or 10 mg/kg) vs. vehicle group (ANOVA, Bonferroni post hoc); #p < 0.016 for SP600125 (3 or 10 mg/kg) vs. vehicle group (ANOVA, Bonferroni post hoc)