Figure 3.

Effect of coadministration of morphine and clonidine on motor function. (a) Saline-treated SPARC-null animals perform better on the rotarod assay compared to WT mice, indicative of an absence of motor impairment in SPARC-null mice. (b), (b′) In SPARC-null mice (b), morphine (●) and clonidine (■) dose-dependently caused motor impairment when administered systemically either alone or coadministered (i.p.) at a constant dose ratio of 100 : 1 (morphine : clonidine). In WT mice (b′), morphine (●) and clonidine (■) dose-dependently caused motor incoordination when administered systemically, but the combination lacked efficacy. (c) Isobolographic analysis applied to the data from Figure 1(b). The y-axis represents the ED₅₀ for morphine, and the x-axis represents the ED₅₀ for clonidine. The lines directed from each ED₅₀ value toward zero represent the respective lower 95% confidence limits of each ED₅₀. The line connecting these two points is the theoretical additive line. The open circle on the theoretical additive line represents the calculated theoretical ED₅₀ value of the combination if the interaction is additive. The observed combination ED₅₀ (●) was not significantly different (t-test) from the theoretical additive ED₅₀ (∘), indicating that the interaction is additive. Isobolographic analysis was not performed in WT mice since the combination lacked efficacy in this assay. Error bars represent ±SEM for each dose point (n = 5–11 animals/dose). See Table 1 for ED₅₀ values. ***P < 0.0001.