Effects of chronic treatment with caffeine on behaviour and related parameters in male and female mice.

: The effects of chronic free access to caffeine (0.01% or 0.05%) in drinking water and subsequent withdrawal on spontaneous motor activity for 24 hours and some related parameters were examined in 8-week-old male and female ICR mice. In the males, the 0.01% group showed little response, but in the 0.05% group the activities in both light- and dark-phases and, consequently, in total increased and peaked on day 5 of treatment. The response gradually decreased on days 15 and 30 and reached the control level after 30 days of caffeine withdrawal. Meanwhile, in the females, the activity was stimulated by both 0.01% and 0.05% of caffeine, at the dark- and light-phases in the former and latter, respectively. The response peaked at 30 days and decreased near to the control level thereafter in both groups. Caffeine affected little the food intake; however, water intakes were higher and lower than the control in the 0.05% and 0.01% male groups, respectively, but the opposite was true in the females. Plasma component levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol and glucose were higher than the control in the males and females treated with 0.05% of caffeine. The caffeine had little effect on the body weight change, organ weights and external appearance throughout the experiment. Thus, the sex- and dose-related differences in the responses to caffeine of spontaneous motor activity and related parameters were proved under physiological conditions.