在慢性应激小鼠模型上评价胍丁胺的抗抑郁作用及机制

目的在小鼠慢性应激抑郁动物模型上评价胍丁胺的抗抑郁作用及其作用机制。方法以慢性应激抑郁模型检测胍丁胺的抗抑郁活性，以western blot方法检测脑源性神经营养因子（brain—derived neurotrophic factor，BDNF）、细胞外信号调节激酶（extracellular signal—regulated kinase，ERK）、cAMP反应元件结合蛋白（cAMP response element—binding protein，CREB）的表达。结果慢性应激导致小鼠探究行为和自发活动减少，表现为测定时间内的活动总路程和活动时间明显减少，新奇抑制摄食潜伏期延长，伴随给予胍丁胺（10、20mg·kg^-1，灌胃）和阳性对照药丙咪嗪（10mg·kg^-1，灌胃）均能够逆转这种改变。同时慢性应激导致海马BDNF、pERK、pCREB表达下调，伴随给予胍丁胺或丙咪嗪可逆转之。结论胍丁胺在慢性应激小鼠抑郁模型上具有抗抑郁作用，此作用与上调海马BDNF及其上、下游信号通路相关激酶，即神经营养通路密切相关。

Evaluation of the Antidepressant-like Effect of Agmatine in Chronically Stressed Mice

Aim To explore the antidepressant-like effect and mechanism of agmatine in chronically stressed mice. Methods The antidepressant-like effect of agmatine was evaluated by using the chronic stress model in mice. Western blot was used for measuring the expression of brain-derived neurotrophic factors （BDNF） , extracellular signal-regulated kinase （ERK） and cAMP response element-binding protein （ CREB ）. Results The open-field exploratory behavior and locomotor activity were significantly decreased, while the latency to feed in novelty-sup- pressed feeding tests increased in chronically stressed mice. Co-administration of agmatine （10,20mg·kg^-1, ig）or imipramine（ 10·kg^-1,ig） reversed those effects. Furthermore, chronic stress also down-regulated the level of BDNF, pERK, pCREB protein expression in hippocampus, while co-administration of agmatine or imipramine blocked such effect. Conclusion Agmatine produced antidepressant-like effect in the chronically stressed model in mice, which may be closely mediated by up-regulation of BDNF, pERK, pCREB. So the antidepressant-like effect of agmatine may be related to the neurotrophic signaling cascade.