Figure 4.

Hyperalgesia, analgesia, tolerance, and respiratory depression. Paw withdrawal threshold in the four strains of rats at baseline (prior to self-administration) and during acute withdrawal (after 14 self-administration sessions), expressed as force (panel A). Paw withdrawal force during acute withdrawal after self-administration is expressed as a function of the baseline paw withdrawal force, as a measure of hyperalgesia (panel B). To measure sensitivity to a noxious stimulus, tail withdrawal latency during the warm water tail immersion test before self-administration and without oxycodone administration is shown in panel C. The tail withdrawal latency after 0.45 mg/kg oxycodone administration both at baseline (before self-administration) and after 14 sessions of oxycodone self-administration are shown as measures of sensitivity to and tolerance to oxycodone, respectively (panel D). Oxygen saturation levels before and after administration of 1 mg/kg oxycodone, taken before self-administration began, as proxies of respiratory depression (panel E). The percent decrease in oxygen saturation after oxycodone administration compared to baseline immediately prior is shown for the oximeter studies conducted before and after 14 self-administration sessions (panel F). Statistical significance between strains is represented as * for p < 0.05 or *** for p < 0.001 in panels B and C. Statistical significance between tests conducted before and after oxycodone self-administration is represented as * for p < 0.05 or *** for p<0.001in panels D and F. Statistically significant differences between oxygen saturation levels before and after acute oxycodone administration is presented as *** for p < 0.001 in panel E.