Research Paper Volume 13, Issue 11 pp 14729—14744

Long-term exposure to polypharmacy impairs cognitive functions in young adult female mice

Effect of polypharmacy regimen on locomotion, coordination and strength, and evaluation of anxiety-like behavior. (A) Locomotor and explorative activity: histograms express horizontal and vertical activity (rearing) assessed in OF cages and analyzed per time intervals over a total duration of 30 minutes. (B) Representative map of the pattern of movements in a control and polypharmacy mouse during the 30-min trial in OF cages. (C) average of latency to fall measured over the 3-trial session of Rotarod test. Interaction between time and treatment groups were analyzed with two-way ANOVA repeated measurements; ***p≤0.001, trial 1 vs trial 3 in control group. (D) Dot histograms show the forelimb strength average measured by Grip Strength test in control and polypharmacy animals. (E) DLB test: dot plots express first latency to enter the LB and time spent by the mice moving in that area. (F) EPM test: number of entries and duration % of time spent in closed arms over the 5 min/trial. (G) Representative heatmaps of the EPM, where red zones display the area that the mice explored the most (average of control and polypharmacy group maps). Ctrl= control, Poly= polypharmacy, n= 10 animals per group. All data are presented as mean ± SEM.

Figure 2. Effect of polypharmacy regimen on locomotion, coordination and strength, and evaluation of anxiety-like behavior. (A) Locomotor and explorative activity: histograms express horizontal and vertical activity (rearing) assessed in OF cages and analyzed per time intervals over a total duration of 30 minutes. (B) Representative map of the pattern of movements in a control and polypharmacy mouse during the 30-min trial in OF cages. (C) average of latency to fall measured over the 3-trial session of Rotarod test. Interaction between time and treatment groups were analyzed with two-way ANOVA repeated measurements; ***p≤0.001, trial 1 vs trial 3 in control group. (D) Dot histograms show the forelimb strength average measured by Grip Strength test in control and polypharmacy animals. (E) DLB test: dot plots express first latency to enter the LB and time spent by the mice moving in that area. (F) EPM test: number of entries and duration % of time spent in closed arms over the 5 min/trial. (G) Representative heatmaps of the EPM, where red zones display the area that the mice explored the most (average of control and polypharmacy group maps). Ctrl= control, Poly= polypharmacy, n= 10 animals per group. All data are presented as mean ± SEM.