Fig. 2.

Assessment of cross-tolerance between morphine and IBNtxA. Analgesic cross-tolerance was assessed in groups of rats, each implanted with either three morphine (n = 4) or placebo (n = 10) pellets and tested with IBNtxA 72 hours later. (A) The next day cumulative morphine dose-response curves revealed a morphine ED₅₀ of 20.5 mg/kg (95% confidence interval [CI], 7.7–54) in the morphine-pelleted rats compared with 3.3 mg/kg (95% CI, 2.7–4.0) in placebo-pelleted animals (P < 0.001). (B) After the morphine cumulative dose-response testing, animals received naloxone (1 mg/kg s.c.). Morphine-pelleted animals displayed a significantly greater number of wet-dog shakes relative to placebo-pelleted controls (P < 0.005). (C) In morphine-pelleted animals, the ED₅₀ for IBNtxA was 0.26 mg/kg (95% CI, 0.15–0.45) compared with 0.52 mg/kg (95% CI, 0.37–0.75) in the placebo-pelleted rats. %MPE, percentage of maximum possible effect.