Yin Yong-Qin, Zhang Chun, Wang Jian-Xin, Hou Jia, Yang Xu, Qin Jing
Department of Traditional Chinese Medicinal Chemistry, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
Food Funct. 2015 Feb;6(2):479-91. doi: 10.1039/c4fo00702f.
Strong evidence has shown that caffeine exerts antidepressant-like effects in chronic stress situations by increasing dopamine levels. However, whether caffeine mediates the dopaminergic system and interferes with the resilience to social defeat stress in mice is unknown. The aim of this study is to investigate the role of caffeine in the behavioral responses to social defeat stress and the possible regulatory role of the dopaminergic system. Mice experienced chronic social defeat stress for 10 days. Caffeine was administered intraperitoneally before, during and after social defeat stress. The time spent in interaction zone, social interaction ratio and sucrose preference test was used to measure the social avoidance and anhedonia in mice. The results showed that chronic pretreatment with caffeine for 14 days and for 10 days during stress reversed the avoidance of social behavior and anhedonia induced by social defeat stress in mice, suggesting the enhancement of the resilience to social defeat stress induced by caffeine. However, neither the treatment with caffeine only during the social defeat stress for 10 days nor the treatment with acute caffeine after defeat stress altered the resilience to stress. Furthermore, chronic caffeine treatment did not affect the normal locomotor activity and the desperate behavior in naïve mice. Moreover, the antagonism of dopamine D1 receptor and not D2 receptor reversed the effect of caffeine on the social avoidance and depressive-like behavior. Finally, pretreatment with higher doses of caffeine did not affect the behavioral response to social defeat stress. Taken together, our findings provide new insight into the effects of caffeine on social avoidance and anhedonia in mice. In addition, our results illustrated the value of measuring changes in depressive-like behavior before and after social defeat stress to determine the potential treatment of caffeine on depression through the regulation of dopaminergic system.
有力证据表明，咖啡因在慢性应激情况下通过提高多巴胺水平发挥类似抗抑郁的作用。然而，咖啡因是否介导多巴胺能系统并干扰小鼠对社会挫败应激的恢复力尚不清楚。本研究的目的是探讨咖啡因在对社会挫败应激的行为反应中的作用以及多巴胺能系统可能的调节作用。小鼠经历了10天的慢性社会挫败应激。在社会挫败应激之前、期间和之后腹腔注射咖啡因。使用在互动区花费的时间、社会互动比率和蔗糖偏好测试来测量小鼠的社会回避和快感缺失。结果表明，在应激期间用咖啡因进行14天和10天的慢性预处理可逆转小鼠因社会挫败应激诱导的社会行为回避和快感缺失，表明咖啡因增强了对社会挫败应激的恢复力。然而，仅在社会挫败应激期间用咖啡因处理10天或在挫败应激后用急性咖啡因处理均未改变对应激的恢复力。此外，慢性咖啡因处理不影响未处理小鼠的正常运动活动和绝望行为。而且，多巴胺D1受体而非D2受体的拮抗作用逆转了咖啡因对社会回避和抑郁样行为的影响。最后，用更高剂量的咖啡因预处理不影响对社会挫败应激的行为反应。综上所述，我们的研究结果为咖啡因对小鼠社会回避和快感缺失的影响提供了新的见解。此外，我们的结果说明了测量社会挫败应激前后抑郁样行为变化以确定咖啡因通过调节多巴胺能系统治疗抑郁症的潜力的价值。
