(A) Schematic timeline of acute tolerance paradigm. Mice were treated with high dose morphine (100 mg/kg s.c.) or high dose oxycodone (80 mg/kg s.c.) or saline; 16 hrs later baseline hotplate plate latencies are assessed. Mice were then injected with Comp5, or MS1, or vehicle immediately after hot plate baseline assessment and 30 min later injected with 10 mg/kg s.c. morphine or 3.5 mg/kg s.c. oxycodone, respectively. Data are plotted as % MPE. (B) Comp5 shows no significant effect on acute analgesic tolerance to morphine in the hot plate assay (F(3, 30)= 12.32 , p<0.0001, ****p<0.0001, *** p<0.001, *p<0.05 (n= 6-9 per group)). (C) Likewise, MS1 demonstrate no significant effect on acute analgesic tolerance to oxycodone in the hot plate assay (F(3, 31)= 17.32, p<0.0001, ****p<0.0001, *** p<0.001, *p<0.05 (n=6-9 per group)). MS1, Comp5, or vehicle were injected i.p. and all opioids were injected s.c.