Figure 4

J147 and donepezil in a scopolamine induced model of memory impairment. C57BL6/J male mice aged eight weeks were assigned to five groups, 12 mice per group, and treated with compounds in their food for two weeks. Groups included J147 (200 ppm), donepezil (20 ppm), combination of J147 and donepezil (200 ppm and 20 ppm, respectively) and two control groups. Memory impairment was induced with scopolamine at 1 mg/kg 30 minutes before behavior testing in all groups except one of the control groups, which received saline as a control. Mice were analyzed for working memory by the Y-maze, for spatial memory by the two-day water maze, and hippocampal dependent memory by fear conditioning. (A) Scopolamine significantly decreased the percent of spontaneous alternations made by mice compared to saline-injected control. Treatment with J147 and donepezil alone, as well as the drugs together, prevented this decrease. (B) Treatment with scopolamine significantly increased the time taken to find the platform compared to saline controls in the two day water maze. J147 prevented the loss in spatial working memory, whereas donepezil did not. (C) On Day 2 of the fear conditioning assay the amount of time freezing in response to the environment is measured as contextual memory. Scopolamine significantly decreased the freezing response and while J147 did increase the freezing response compared to scopolamine it was not significant. However the J147 and donepezil together did appear to have a synergistic effect. (D) On Day 3 the amount of time freezing in response to the tone is measured as emotional memory. Scopolamine significantly decreased the freezing response. While J147 and donepezil alone did increase the freezing response compared to scopolamine, it was not significant. However, J147 and donepezil together had a synergistic effect with the combination significantly increasing the freezing response compared to scopolamine control. One-way ANOVA with Tukey post hoc test, P-value, *P <0.05, **P <0.01, and ***P <0.001. All data shown are means ± SD, N = 7 to 8 per group.