TABLE 1.

Impact of pharmacological manipulations (see Figure 4A) on morphine antinociception in the tail-flick test.

Treatment	Day 1	Day 9	ED50 Shift
Vehicle	10.62 (8.034 – 14.04)	20.15 (11.21 – 36.21)	1.90
Morphine (10)	7.874 (6.273 – 9.884)	141.2 (44.34 – 449.7)*	17.93
GAT211 (20)	8.143 (6.441 – 10.29)	17.09 (11.43 – 25.57)*	2.09
GAT211 (20) + morphine (10)	8.981 (6.524 – 12.36)	55.70 (33.96 – 91.37)*	6.20

Tail-flick latencies did not differ between groups on day one of cumulative dosing. A right-ward shift in the ED₅₀ for producing tail-flick antinociception was observed for animals receiving repeated injections of either morphine (10 mg/kg/day i.p.), GAT211 (20 mg/kg/day i.p) or the combination of morphine (10 mg/kg/day i.p.) with GAT211 (20 mg/kg/day i.p), but not vehicle. The most pronounced shift in the ED₅₀ was observed in animals treated with morphine (10 mg/kg i.p.) once daily for 7 days. Animals co-treated with morphine (10 mg/kg i.p.) and GAT211 (20 mg/kg i.p.) displayed a reduced right-ward shift relative to animals treated with morphine alone. Data are expressed as ED₅₀ (Confidence Interval, CI), generated from linear regression analysis. ED₅₀ doses in mg/kg i.p. with 95% confidence intervals (CI) are shown.