Moreover, acquisition of a passive avoidance response has been used to measure long-term memory of an aversive experience. In Fig. 4, a significant group effect was found on step-through latency in retention trial with scopolamine [H (9) = 32.69, p < 0.001]. The step-through latency time of the scopolamine-treated group was significantly shorter than that of the control group (p < 0.001). In contrast, the step-through latency time for the donezepil-treated group was higher than that of the scopolamine-treated group (p < 0.01). The shorter step-through latency time induced by scopolamine was improved by RG, Rg3 (20 mg/kg and 40 mg/kg, p < 0.05). A previous
study has documented the memory enhancing effects Rg3 on scopolamine-induced cognitive deficit PARP inhibitor in the passive avoidance task [18]. Importantly, ginseol Selleckchem ABT-263 k-g3 (25 mg/kg, 50 mg/kg, 100 mg/kg and 200 mg/kg) also recovered scopolamine-induced amnesia. Altogether, these findings indicate that RG, Rg3 and the Rg3-enriched fraction, ginseol k-g3, affect conditioning and/or associative memory. Considering that ginseol k-g3, and also Rg3 and RG, significantly improved scopolamine-induced memory impairment in mice in the passive avoidance but not in the Y-maze task, it could be hypothesized that these substances
modulate long-term but not short-term or working memory. To verify the selective memory (i.e., long-term) enhancement capacity of ginseol k-g3 in mice, we measured the effects of ginseol k-g3 on scopolamine-induced memory deficits in the Morris water maze task. The water maze test is another widely used behavioral assay to measure hippocampus-dependent
long-term and spatial memory [36] and [37]. In this test, decrease in escape latency observed from day to day in the first trial represents long-term memory, while that from the first trial to the second trial represents working or short-term memory [37]. Moreover, the time in the quadrant with the platform indicates changes in spatial memory [37] and [38]. The escape latencies of mice during the second trial sessions across the training days were tabulated. Fig. 5A shows that escape latencies in groups given vehicle (control) or scopolamine, with or without the test drugs, varied significantly with respect to day [F (4,448) = 33.10, p < 0.001] and treatment [F (9,448) = 8.91, over p < 0.001]. Two-way ANOVA, however, did not show significant interaction between day and treatment. In contrast to the vehicle-treated groups (Control), scopolamine-treated mice consistently exhibited longer escape latency across the training days consistent with our previous observations [29]. Furthermore, treatment of ginseol k-g3 at a dose of 50 mg/kg significantly attenuated scopolamine-induced delay in escape latency during Day 4 and Day 5 of training (p < 0.05). The 200 mg/kg dose of ginseol k-g3 also shortened escape latency during Day 5 of training (p < 0.05).