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Antidepressant-like effects of Xiaochaihutang in a rat model of chronic unpredictable mild stress

Su, Guang Yue, Yang, Jing Yu, Wang, Fang, Ma, Jie, Zhang, Kuo, Dong, Ying Xu, Song, Shao Jiang, Lu, Xiu Mei, Wu, Chun Fu
Journal of ethnopharmacology 2014 v.152 no.1 pp. 217-226
animal models, antidepressants, dopamine, electrochemistry, food consumption, high performance liquid chromatography, hippocampus, immunohistochemistry, mechanism of action, nerve growth factor, neurotransmitters, rats, receptors, serotonin, staining, sucrose, therapeutics, traditional medicine, China
Xiaochaihutang (XCHT) has been used in China for thousands of years to treat “Shaoyang syndrome”, which involves depressive-like symptoms. However, few studies have investigated its antidepressant effects and pharmacological mechanism of action. The present study was designed to confirm the antidepressant effect of XCHT using a chronic unpredictable mild stress (CUMS) model and explore its potential mechanism of action by investigating the monoamine neurotransmitters (dopamine and 5-hydroxytryptamine) and neurotrophins (BDNF and NGF).The CUMS model was established in rats, and the antidepressant effect of XCHT (0.6, 1.7 and 5mg/kg/day, given by gastric gavage for 4 weeks) was investigated using the open field test (OFT), food consumption test and sucrose preference test. The concentrations of 5-HT and DA in the hippocampus were measured by high performance liquid chromatography with electrochemical detection (HPLC-ECD). The expressions of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and their receptors tyrosine receptor kinase B (TrkB) and tyrosine receptor kinase A (TrkA) in the hippocampus were measured by immunohistochemical staining analysis.CUMS caused a significant decrease in OFT, food consumption and sucrose preference in rats, and these depression-like behaviors were significantly improved by XCHT (1.7 and 5g/kg/day). Moreover, XCHT significantly increased the concentrations of 5-HT (0.6 and 5g/kg/day) and DA (5g/kg/day), and improved the BDNF, NGF, TrkB and TrkA expressions in the hippocampus (1.7 and 5g/kg/day), which was reduced in CUMS rats.The results obtained suggested that XCHT may have therapeutic actions on depression-like behavior induced by CUMS in rats possibly mediated by increasing the monoamine neurotransmitter concentration and neurotrophin expression in the hippocampus.