Figure 4

Evaluation of learning and memory in 24r-mTBI and 5r-mTBI mice. Anatabine treatment improved spatial memory deficits in the 24r-mTBI but not 5r-mTBI mice. In the 24r-mTBI cohort, 24r-mTBI-vehicle mice exhibited longer cumulative distance ((A); p < 0.05), distance traveled ((B); p < 0.05), and latency to enter the box on days 4–6 (C) compared to 24r-sham vehicle during the acquisition trial. Similarly, in the 5r-mTBI cohort, 5r-mTBI-vehicle mice exhibited longer cumulative distance ((E); p < 0.05), distance traveled ((F); p < 0.001), and latency to enter the box on days 3–6 (G) compared to 5r-sham vehicle. 24r-mTBI-anatabine mice showed a decrease in cumulative distance ((A); p < 0.05), distance traveled ((B); p < 0.05) and latency (C) compared to 24r-mTBI- vehicle mice. Anatabine did not attenuate memory deficits in the 5r-mTBI-anatabine group during the acquisition trial. During the probe trial, 24r-mTBI increased mean time to target zone compared to sham-vehicle mice ((D); p < 0.001), which was decreased in the 24r-mTBI-anatabine mice vs 24r-mTBI ((D); p < 0.001). In the 5r-mTBI group, 5r-mTBI-vehicle mice had an increase in mean time compared to 5r-sham-vehicle ((H); p < 0.05) but no anatabine induced decrease was detected in the 5r-mTBI-anatabine mice, however the trend is present. Latency in 5r-mTBI-anatabine mice was not significantly different from the 5r-sham-vehicle mice (p = 0.082). Statistical significance for the cumulative distance and distance traveled were analyzed using MANOVA; the mean time to target hole was analyzed using one-way ANOVA.