Dose-related antinociception induced by morphine sulfate in 12-week-old wild-type (+/+) and A2A receptor knock-out (−/−) mice. a, Time course of morphine-induced antinociception in the +/+ mice; b, time course of morphine-induced antinociception in the −/− mice measured as tail immersion latency at 55°C. ○, Saline control values; ●, 1 mg/kg morphine sulfate; ■, 5 mg/kg morphine sulfate; ▪, 10 mg/kg morphine sulfate; ▵, 20 mg/kg morphine sulfate. Doses (0.1 ml volume, i.p) were administered at 0 min.pretest, Pretest responses 20 min before injection.c, Dose–response relationship for morphine sulfate at peak antinociception (45 min after injection) in wild-type (○) and A2A receptor knock-out (●) mice. Values are means ± SEM of five determinations (n = 5). Differences in dose–response curves between genotypes were not statistically significant (p > 0.05; ANOVA). The difference in tail immersion latencies between +/+ and −/− saline-treated animals was statistically significant (p < 0.05; ANOVA).