Comparing Effects of Caffeine and Theobromine on Adrenal Hypertrophy and Social Behavior in Psychosocial Stressed Mice

Management of chronic psychological stress is important for the prevention of depression, mood disorders, and other related ailments. Recent studies have shown that dietary methylxanthines, such as caffeine and theobromine, exert preventive effects on these ailments. Although the psychological effects of caffeine are well-investigated, those of theobromine are not fully understood. In the present study, the effects of theobromine were evaluated and compared with those of caffeine using a mouse stress model based on confrontational housing. Male mice were kept separately in partition cages (two per cage) to allow the establishment of territories for confrontational housing. The mice were administered caffeine or theobromine daily via oral gavage (6 mg/kg). Thereafter, the partition was removed to induce confrontational stress. We found that theobromine, but not caffeine, suppressed adrenal hypertrophy caused by confrontational stress. Moreover, sociability tests revealed that caffeine and theobromine had different effects on the behavioral changes caused by confrontational stress. Our results suggest that orally administered theobromine suppresses adrenal hypertrophy caused by psychosocial stress and induces different behavioral changes than dose caffeine.