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.
Ibrahim, Micheal K.; Kamal, Mohamed M.; Tikamdas, Rajiv; Nouh, Roua Aref; Tian, Jiang; and Sayed, Mostafa, "Effects of Chronic Caffeine Administration on Behavioral and Molecular Adaptations to Sensory Contact Model Induced Stress in Adolescent Male Mice" (2020). Pharmacy. 535.