(A) Morphine produced a dose-related acute antinociceptive effect in the hotplate test on day 2 in a manner that was not altered by LY2828360 treatment. (B) Following repeated dosing with morphine for 10 days, hotplate antinociception was no longer observed, consistent with the development of morphine tolerance. (C) Comparisons of all doses and treatments on day 2 and day 10 of repeated injections revealed a significant effect of injection day, drug treatment, and the interaction. Morphine (10 mg/kg i.p.) in the presence or absence of LY2828360 produced greater % maximal possible antinociceptive effect (% MPE) compared to day 10 treatment or any other group. Data are expressed as mean ± S.E.M. (n = 6 per group). *P < 0.05, **P < 0.01, two-way ANOVA followed by Bonferroni’s post hoc test.