Dose-related antinociception induced by CI-977 in 12-week-old wild-type (+/+) and A2A receptor knock-out (−/−) mice. a, Time course of CI-977-induced antinociception in the +/+ mice; b, time course of CI-977-induced antinociception in the −/− mice measured as tail immersion latency at 52°C. ○ represents saline control values; ●, 0.01 mg/kg CI-977; ■, 0.03 mg/kg CI-977; ▪, 0.1 mg/kg CI-977; ▵, 0.3 mg/kg CI-977; ▴ 1 mg/kg CI-977. Doses (0.1 ml volume, i.p) are administered at 0 min. pretest, Pretest responses 20 min before injection. c, Dose–response relationship for CI-977 at peak antinociception (10 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 statistically significant (p < 0.05; ANOVA); *p< 0.05 (Scheffe's post hoc analysis). Differences in tail immersion latency between +/+ and −/− saline-treated animals were not statistically significant (p > 0.05; ANOVA).