Department of Developmental Pharmacology, National Organization for Drug Control and Research (NODCAR), Giza, Egypt.
Pharmacology and Biochemistry Department, Faculty of Pharmacy, The British University in Egypt (BUE), El-Sherouk City, Cairo, Egypt.
Behav Genet. 2020 Sep;50(5):374-383. doi: 10.1007/s10519-020-10003-1. Epub 2020 Jun 5.
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，咖啡因通过拮抗神经元腺苷 A2A 受体来减轻应激引起的情绪功能障碍和记忆恶化。然而，咖啡因是否通过调节其他分子靶点来发挥这种作用，这些靶点干扰了青春期雄性小鼠对社会挫败应激的适应能力，目前尚不清楚。本研究旨在探讨咖啡因在感觉接触模型（SCM）诱导的社会应激反应中的作用，以及其对 Na/K ATPase 泵基因表达水平可能的改变。将青春期雄性小鼠暴露于 SCM 中 12 天。SCM 后，每日腹腔内给予咖啡因 14 天。使用互动区时间、社交互动比率、对新物体的偏好指数、开放臂时间和强迫游泳试验中的不动时间来测量小鼠的运动活动、社交回避、短期记忆、焦虑和抑郁。结果表明，慢性 14 天的咖啡因治疗改善了运动活动，逆转了社交回避行为，提高了对新物体的偏好，并逆转了社会挫败应激引起的抑郁，表明咖啡因增强了对社会挫败应激的适应能力。此外，咖啡因治疗确实改变了前额叶皮层和海马体中 Na/K ATPase 同工型的基因表达水平。在大多数情况下，改变的基因表达与观察到的行为变化相关。总之，我们的研究结果为慢性咖啡因给药对暴露于 SCM 的青春期雄性小鼠的运动活动、社交回避、短期记忆和抑郁的影响提供了新的见解。
