Caffeine and sleep-deprivation mediated changes in open-field behaviours, stress response and antioxidant status in mice

OBJECTIVES Effects of daily caffeine consumption on open-field behaviours, serum corticosterone and brain antioxidant levels were investigated after six hours of total sleep-deprivation in prepubertal mice. We tested the hypothesis that daily caffeine consumption may significantly alter behaviour, stress and antioxidative response of prepubertal mice to an acute episode of total sleep-deprivation. METHODS Prepubertal Swiss mice of both sexes were assigned to two main groups of 120 each (subdivided into 6 groups of 10 each, based on sex), and administered vehicle or graded oral doses of caffeine (10, 20, 40, 80 and 120 mg/kg/day) for 14 days. On day 14, a main group was subjected to 6 h of total sleep-deprivation by 'gentle-handling'. Open-field behaviours were then assessed in both groups, after which animals were euthanized, and levels of corticosterone, superoxide dismutase and glutathione peroxidase assayed. RESULTS Horizontal locomotion, rearing and grooming increased significantly, compared to control, with sleep-deprived (SD) mice showing stronger caffeine-driven responses at higher doses; and SD female mice showing sustained response to caffeine, compared to respective males. Plasma corticosterone increased with increasing doses of caffeine in both non sleep-deprived (NSD) and SD mice; although SD mice had higher corticosterone levels. Sleep-deprivation and/or higher doses of caffeine were associated with derangements in brain antioxidant levels. CONCLUSION Repeated caffeine consumption and/or acute sleep-deprivation led to significant changes in pattern of open-field behaviour and stress/antioxidant response in mice. Responses seen in the study are probably due to modulatory effects of caffeine on the total body response to stressful stimuli.