The role of NR2B receptors in acute morphine-induced analgesia and analgesic tolerance. (A) Morphine analgesia was greater in mice pretreated with Ro25-6981 (5 mg/kg, i.p., n = 5) compared to mice pretreated with saline (n = 4) beginning 90 min after injection. There was a significant effect of treatment (p < 0.05) with significant differences occurring at 90, 120, 150 and 180 minutes after injection (p < 0.05 for all). * represents a significant difference from saline injected mice. (B) Response latencies were significantly increased by Ro 256981 injection (5 mg/kg, i.p., n = 8). Day 7 vs. Day 8, p < 0.001). * represents a significant difference from responses on Day 6 and 7. (C) Daily co-administration of Ro 256981 (5 mg/kg, i.p.) with morphine (10 mg/kg, s.c.) attenuates opioid analgesic tolerance (p < 0.001) compared to mice receiving morphine (n = 7) or saline (n = 5). There was no difference between morphine treated and Ro256981+morphine treated mice on Day 1 (p = 0.74) but a significant difference arose on Day 2 (p < 0.001) and persisted during Days 3, 4, 6 and 7 (p < 0.001, p < 0.01, p < 0.05, p < 0.05 respectively).