Effect of chronic administration and withdrawal of caffeine on motor function, cognitive functions, anxiety, and the social behavior of BLC57 mice

Abstract

Objectives: The cognitive functions, motor coordination, and social behavior were studied in rodents after adding different doses of caffeine in their drinking water.

Methodology: BLC57 mice were divided into four groups: Control (n = 8), chronic moderate dose (n = 8, Ch] MD), Ch high dose (n = 8, Ch HD), and withdrawal (n = 8, WD). Caffeine was administered for 1 month to all groups. Spatial memory was tested by Morris water maze, motor coordination by rotarod (RR), social behavior by (Crawley's test), and anxiety by elevated plus maze (EPM) test.

Results: In water maze, the latency to reach the platform was significantly shorter in Ch MD group compared to the control and the Ch HD groups. WD group showed the worst performance. RR results showed that the groups treated with caffeine performed poor in comparison to the control group where their latency to fall was significantly less. In the three-chamber test, the Ch MD group showed enhanced sociability (session 1) and social novelty behavior (session 2). On the other hand, both Ch HD and WD showed a lack in sociability and a deficit in social novelty. In the EPM, results showed that all caffeine administrated mice where more anxious than the control group.

Conclusion: We concluded that chronic administration of caffeine in MD resulted in enhancement of spatial memory, motor functions, sociability, and social novelty. The anxiety in these animals was, however, increased. On the other hand, Ch HD caffeine had opposite effects on all the parameters except for anxiety.

Keywords: Caffeine; anxiety; cognitive functions; motor function; social behavior.

Figure 1

Latency to fall (Mean ± Standard error of means seconds) in the rotarod test for the control, moderate dose (MD), and HD group. The time spent by the caffeine-treated groups was significantly less than the control group (ANOVA test, P < 0.005, F = 5.069079, F crit = 2.636391). Significant differences were recorded when comparing the control group to chronic (Ch) HD (P < 0.01), Ch MD (P < 0.001), WD (P < 0.01) groups. No significant difference was obtained between Ch MD, Ch HD, and WD groups (ANOVA, P = 0.49, F = 0.7069, Fcrit = 3.038)

Figure 2

(a-d) Effect of the administration of caffeine on a mouse model in Morris water maze test to assess spatial memory and learning. The results displayed different levels of cognitive effects based on the chronic doses and withdrawal (WD) of caffeine. Statistical analysis for the latency required by the animals to reach the platform (a) revealed that a significant difference was recorded between the groups (ANOVA P < 0.0005). Two trial t-test calculated a significant difference between the control group and Ch HD (P < 0.05) and WD (P < 0.001) groups. No significant difference was recorded between the Cont group and the Ch MD group (P = 0.15). Figure 2c shows that there are no significant differences between the groups concerning their speed of swimming the pool during testing (ANOVA = 0.3448). In the probe trial (D) ANOVA test between the groups showed a significant difference (P < 0.005). Two trial t-test showed that the control group stayed significantly more time in the platform quadrant than the Ch HD (P < 0.0001) and WD (P < 0.0005) groups. No significant differences between the Cont and the Ch MD groups (P = 0.169). The Ch MD group of animals stayed significantly more time in the platform quadrant than the Ch HD (P < 0.0001) and WD (P < 0.005) groups

Figure 3

The effect of different doses and withdrawal of caffeine on anxiety, assessed by elevated plus Maze test. ANOVA test showed a significant difference between the groups (P < 0.05) in the total time the animals spent in the open arm of the maze. Two trials t-test showed that the control animals stayed significantly more time in the open arm of the elevated plus maze (less anxiety) when compared to the chronic high dose (Ch HD) (P < 0.005) and WD (P < 0.05) groups. No significant difference was recorded between the control and the Ch MD groups (P = 0.279)

Figure 4

Three-chamber test to assess sociability and preference for social novelty. (a) Sociability (Session 1: Time spent in chamber with a mouse vs. chamber without mouse). (b) Preference for social novelty (Session 2: Time spent in chamber with the old mouse vs. chamber with new mouse). Control animals showed normal sociability and preference for social novelty. Within the caffeine-treated groups, only the chronic moderate dose group performed similarly to the control by showing a significant increase in sociability and preference for social novelty (see the text for statistical significances and P values)