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. Author manuscript; available in PMC: 2024 Jan 1.
Published in final edited form as: Pharmacol Res. 2022 Nov 20;187:106560. doi: 10.1016/j.phrs.2022.106560

Figure 11. Co-administration of LY2828360 with morphine prevents the development of tolerance to morphine’s antinociceptive effects in male, and to a lesser extent in female CB2f/f mice but not in advillinCre+/;CB2f/f mice.

Figure 11.

Morphine (10 mg/kg i.p.) alleviated ddC-evoked mechanical (A, C, E, G) and cold (B, D, F, H) responsiveness on days 1 and 3 of administration. Co-administration of LY2828360 (0.03 mg/kg or 0.1 mg/kg i.p.) with morphine (10 mg/kg i.p.) prevented the development of tolerance, producing sustained suppressions of ddC-evoked mechanical (A,C) or cold (B,D) allodynia on days 1-12 of administration in male CB2f/f GFP mice but not male advillincre+/;CB2f/f mice. Co-administration of LY2828360 (0.03 mg/kg or 0.1 mg/kg i.p.) with morphine (10 mg/kg i.p.) lessened the development of tolerance in CB2f/f GFP mice, though to a lesser extant than that observed in male CB2f/f GFP mice (E-H). The tolerance sparing effects of LY2828360 were absent in female advillincre+/;CB2f/f mice (G,H). ###p<0.001 vs. baseline, ***p<0.001 all groups vs. veh+veh, $$$p<0.001, $$p<0.01 MOR+LY0.1 mg/kg and MOR+ LY0.03 mg/kg vs. all other groups, +++p<0.001, ++p<0.01 MOR+Veh vs. Veh+Veh, &&p<0.01, &p<0.05 MOR+LY0.1 mg/kg vs. MOR+LY0.03 mg/kg, @@p<0.01, @p<0.05 MOR+LY0.1mg/kg vs. MOR+Veh, ^^p<0.01 MOR+LY0.1 mg/kg and MOR+LY0.03 mg/kg vs. Veh+Veh, ===p<0.001, =p<0.05 MOR+LY0.1 mg/kg vs. all other groups, %p<0.05 MOR+LY0.03 mg/kg vs. Veh, −p<0.01 MOR+LY0.03 mg/kg vs. Veh+Veh and MOR+LY0.1 mg/kg. :::p>0.001, ::p>0.01, :p>0.05 CB2f/f MOR+LY vs. all other groups, >p<0.05 CB2f/f MOR+LY vs. CB2f/f MOR+Veh, !p<0.05 CB2f/f MOR+Veh vs. Adv cre+;CB2 f/f MOR+LY, <<p<0.01, <p<0.05 CB2f/f MOR+Veh vs. all other groups, \p<0.05 CB2f/f MOR+LY vs. vs. advillincre+/;CB2f/f MOR+VEH, −p<0.05 CB2f/f vs. advillincre+/;CB2f/f MOR+LY, “p<0.05 CB2f/f vs. advillincre+/;CB2f/f, ~p<0.05 CB2f/f MOR+LY vs. advillincre+/;CB2f/f MOR+LY, /p<0.05 CB2f/f MOR+Veh vs. advillincre+/;CB2f/f MOR+LY. Two-way ANOVA, Tukey Multiple comparisons test post-hoc. (N=6-10 per group). Black bars indicate period of LY and morphine co-administration. MOR: morphine, LY: LY2828360, Veh: vehicle.