Previous studies have shown that caffeine attenuates stress-induced mood dysfunction and memory deterioration through neuronal adenosine A2A receptors antagonism. However, whether caffeine exerts this effect through modulating other molecular targets, which interfere with the resilience to social defeat stress in adolescent male mice is unknown. This study was conducted to investigate the role of caffeine in the behavioral responses to social stress induced by the sensory contact model (SCM) and the possible alteration of the gene expression level of Na/K ATPase pump. Adolescent male mice were exposed to SCM for 12 days. Caffeine was administered intraperitoneal daily for 14 days after SCM. The time spent in interaction zone, social interaction ratio, preference index to novel objects, time spent in the open arms and immobility time in forced swimming test were used to measure the locomotor activity, social avoidance, short-term memory, anxiety and depression in mice. The results showed that chronic treatment with caffeine for 14 days improved locomotor activity, reversed the avoidance of social behavior, improved preference to novel objects, and reversed depression induced by social defeat stress in adolescent male mice, suggesting the enhancement of the resilience to social defeat stress induced by caffeine. Moreover, caffeine treatment did alter gene expression levels of Na/K ATPase isoforms in both prefrontal cortex and hippocampus. Altered gene expression was significant in most cases and correlates with the observed behavioral changes. Taken together, our findings provide new insight into the effects of chronic caffeine administration on locomotor activity, social avoidance, short-term memory and depression in adolescent male mice exposed to SCM.

先前的研究表明，咖啡因可通过神经元腺苷A2A受体拮抗作用减轻应激引起的情绪障碍和记忆力衰退。然而，咖啡因是否通过调节其他分子靶标来发挥这种作用，而这些靶标干扰了青春期雄性小鼠对社交挫败压力的抵抗力。进行这项研究以调查咖啡因在由感官接触模型（SCM）诱导的对社会压力的行为反应中的作用以及Na / K ATPase泵基因表达水平的可能改变。将青春期的雄性小鼠暴露于SCM中12天。SCM后每天腹膜内给予咖啡因14天。在互动区花费的时间，社交互动率，对新颖对象的偏好指数，张开双臂的时间和强迫游泳的不动时间用于测量小鼠的运动能力，社交回避，短期记忆，焦虑和抑郁。结果表明，长期使用咖啡因治疗14天可改善运动能力，逆转社交行为的避免，改善对新事物的偏好，并逆转青春期雄性小鼠因社交挫败压力引起的抑郁，这表明社交挫折的抵抗力增强咖啡因引起的压力。此外，咖啡因治疗确实改变了额叶前皮质和海马中Na / K ATPase亚型的基因表达水平。在大多数情况下，基因表达的改变很明显，并且与观察到的行为改变有关。在一起