Figure 4.

Effects of pretreatment with naltrexone on morphine-induced changes in schedule-controlled responses and thermal nociception. Pretreatment with either 0.032 mg/kg naltrexone (upward-facing open triangles) or 1 mg/kg naltrexone (open squares) antagonizes the dose-response effect of morphine with vehicle pretreatment (filled circles), to dose-dependently A. decrease schedule-controlled behavior, and B., increase thermal latency. Meanwhile, pretreatment with either 0.032 mg/kg naltrexone (upward-facing open triangles) or 1 mg/kg naltrexone (open squares) does not antagonize the dose-response effect of mitragynine with vehicle pretreatment (filled circles), to dose-dependently C. decrease schedule-controlled behavior, and D., increase thermal latency. Abscissae: drug dose (mg/kg, I.P.), log scale. Ordinates: A, C: Percent control rates of food-maintained responding. B, D: Percent maximum possible effect (MPE). Each point represents the mean ± S.E.M. of data points for 16 subjects (eight males and eight female for morphine alone and in combination with 0.032 mg/kg naltrexone and mitragynine alone and in combination with 0.032 mg/kg naltrexone), 12 (six males and six female for morphine in combination with 1.0 mg/kg naltrexone), and 13 (seven males and six female for mitragynine in combination with 1.0 mg/kg naltrexone). **P < 0.01, and ***P < 0.001 vs. data during the first cycle (i.e., either vehicle or naltrexone). The morphine control is re-plotted from Figure 2.