Dose response and time course effects of LY-2456302 on U50,488-induced analgesia in the warm water tail flick assay (TFA). (a) LY-2456302 was administered orally (p.o.) 1 hour prior to injection of U50,488 (30 mg/kg, i.p.), and TFA latencies were determined 1 hour after U50,488 administration. n = 12 (0.0 mg/kg), 6 (0.1 mg/kg), 7 (0.3 mg/kg), 6 (1.0 mg/kg), 6 (3.0 mg/kg), and 8 (10.0 mg/kg). *P < .05 compared withLY-2456302 (0.0 mg/kg). (b) Based on the dose response, nonlinear regression was used to determine the AD80 dose, which was then used to test the ability of LY-2456302 to attenuate U50,488-induced analgesia when administered 1 hour (n = 18), 2 hours (n = 16), 4 hours (n = 12), 8 hours (n = 7), and 24 hours (n = 12) prior to the TFA test. LY-2456302 (0.9 mg/kg, p.o.) significantly reduced U50,488-induced increases in TFA latency when administered 1 hour before the TFA test. *P < .05 compared withVeh. (c) For each LY-2456302 pretreatment time point, a separate vehicle (3% lactic acid in water) group was tested; total n = 38. There was no effect of Veh pretreatment on TFA latency at any time. As such, Veh groups for each time point were collapsed for the analysis shown in (b).