3.1 Chronic caffeine treatment extended circadian activity period in WT.
We administered 0.05% caffeine to WT (n=7) under LD. After 7 days, the caffeine-treated and control (n=6) mice were moved to DD. For 21 days in DD, the activity period of caffeine-treated mice (23.85±0.022 h, Figure 1a) was longer than that of controls (23.72±0.032 h, Figure 1b). After replacing caffeine by water, the period did not shorten for 26 days, and caffeine re-administration for 21 days extended this period (Figure 1a, 1c upper, one-way ANOVA P=0.008). In the control mice, caffeine administration was started at day 21 in DD. Caffeine treatment for 26 days extended the period, as previously reported (Oike et al., 2011). After replacing caffeine by water, the period did not shorten for the following 21 days (Figure 1b, 1c lower, one-way ANOVA, P=0.003).