Figure 4.
Effect of coadministration of morphine and clonidine on overall activity. (a) Saline-treated SPARC-null animals do not differ from WT mice in the number of peripheral squares covered in the open field, indicative of comparable overall activity between the two strains. (b), (b′). Both in SPARC-null (b) and WT (b′) mice, morphine (●) caused an increase in activity, while clonidine (■) dose-dependently caused sedation. When coadministered (i.p.) at a constant dose ratio of 100 : 1 (morphine : clonidine), the combination showed no efficacy in SPARC-null mice and produced hyperactivity in WT mice. No isobolographs were plotted for either strain as the drugs had opposing effects. Error bars represent ±SEM for each dose point (n = 5–11 animals/dose). See Table 1 for ED50 values.