Figure 4.

Effects on pretreatment with SL327 and MK2206. We evaluated the effects of SL327 (30 mg/kg) and MK2206 (60 mg/kg) on the duration of immobility during the FST and the levels of phosphorylated mTOR, Akt, and ERK in the hippocampus of mice treated with danshensu (10 mg/kg). The timeline for the FST under different treatment conditions is shown (A). Pretreatment with SL327 and MK2206 prevented the danshensu-induced reduction in the duration of immobility during the FST (B; analysis of variance; F[3,28]=31.316; p<0.001; N=8 per group). Compared with saline treatment: Tukey post hoc analysis. Western blotting was performed to evaluate the activation of mTOR, Akt, and ERK (C). Densitometric analyses of the blots (normalized to β-actin levels) confirmed the increased levels of phosphorylated mTOR (D), Akt (E), and ERK (F) in mice treated with danshensu. Pretreatment with SL327 and MK2206 prevented the danshensu-induced increase in the level of phosphorylated mTOR (D). Pretreatment with MK2206, but not SL327, prevented the danshensu-induced increase in the level of phosphorylated Akt (E). Furthermore, pretreatment with SL327, but not MK2206, prevented the danshensu-induced increase in the level of phosphorylated ERK (F). No significant between-group difference was observed in the level of total Akt, ERK, or mTOR. N=4 per group. Between- group comparisons were performed using the nonparametric Kruskal–Wallis test, followed by the Conover–Iman post hoc test. Data are presented in terms of the mean±standard error of the mean values. *p<0.05; **p<0.01; ***p<0.001. FST, forced swimming test; p-mTOR, phosphorylated mTOR; mTOR, mammalian target of rapamycin; p-Akt, phosphorylated Akt; Akt, protein kinase B; p-ERK, phosphorylated ERK; ERK, extracellular signal-regulated kinase.