Fig. 4.
Reversal effects of single intrathecal injection of d-amino acid oxidase inhibitors on established morphine antinociceptive tolerance in the rat formalin test (A). Rats received intrathecal injections of saline (10 μl) or morphine (50 μg) twice daily for 5 days. On the sixth day, rats were challenged by a single-bolus intrathecal injection of saline (10 μl) or morphine (5 μg) 20 min before formalin test. 5-Chloro-benzo[d]isoxazol-3-ol (CBIO; 30 μg), AS057278 (100 μg), and sodium benzoate (300 μg) were injected 12 h earlier before morphine challenge to avoid their acute antinociceptive effects. Nociceptive behavior was quantified by counting the number of the formalin-injected paw flinches in 1-min epochs. (B and C) Represent acute phase nociception and tonic phase pain measured by areas under curve over 10–90 min (AUC10–90 min), respectively. Data are presented as means ± SEM (n = 6 in each group). *, #, + Denote statistically significant difference from the saline + saline + saline group, saline + saline + morphine group, and morphine + saline + morphine group, respectively (P < 0.05 by one-way ANOVA followed by post hoc Student–Newman–Keuls test).