Fig. 4

BTZ effect on P-gp transport-dependent nociception in hAPP mice in vivo. A Picture of a mouse placed on the LE 7106 Light Beam analgesia meter (Harvard Apparatus, Holliston, MA, USA). B Tail flick latency times at 30, 60, 120, 180, and 360 min after loperamide dosing (5 mg/kg; s.c.); maximum possible effect (MPE%) plotted against time. WT mice (n = 10) flicked their tails shortly after the radiant stimulus was applied, indicating that loperamide has no central antinociceptive effect. P-gp KO mice (n = 9) and WT that received the P-gp inhibitor CSA (50 mg/kg; i.p.; n = 11) displayed high MPE% values indicating loperamide had a central antinociceptive effect in these animals. Symbols indicate statistical groupings of pairwise comparisons adjusted for FDR (false discovery rate) at each time point. No symbols indicate no significant differences among any treatments. Points that share a symbol do not significantly differ from each other. C The area under the curve (AUC) for the time course was fourfold higher in CSA-treated WT mice and eightfold higher in P-gp KO mice compared to WT mice. The difference in AUCs for P-gp KO mice and CSA-treated WT mice was not statistically significant, although both significantly differed from WT mice. Symbols indicate statistical groupings of pairwise comparisons adjusted for FDR. Columns that share a symbol do not significantly differ from each other. D The MPE% in WT mice and BTZ-treated hAPP mice was comparable, whereas hAPP mice and hAPP mice treated with BTZ-CSA had significantly higher MPE% values. Symbols indicate pairwise comparisons adjusted for FDR at each time point (30, 60, 120, and 180 min). Points that share a symbol do not significantly differ from each other. E The AUC between WT and BTZ-treated hAPP mice was comparable. AUC values for hAPP mice were significantly higher than those of WT mice. The highest AUC value was observed for hAPP mice treated with BTZ/CSA. Symbols indicate statistical groupings of pairwise comparisons adjusted for FDR. Columns that share a symbol do not significantly differ from each other. Data per group are shown as mean ± S.E.M for each animal: WT: n = 10, hAPP: n = 10, hAPP-BTZ: n = 10, hAPP-BTZ + CSA: n = 10