Anxiolytic effect of a herbal medicine, yokukansan, in aged rats: Involvement of serotonergic and dopaminergic transmissions in the prefrontal cortex
Anxiolytic effect of a herbal medicine, yokukansan, in aged rats: Involvement of serotonergic and dopaminergic transmissions in the prefrontal cortex
复制标题
DOI：
10.1016/j.jep.2009.09.048
复制
发表时间：
2010-01-08
影响因子：
5.4
通讯作者：
Tabira, Takeshi
中科院分区：
文献类型：
--
作者：
Mizoguchi, Kazushige;Tanaka, Yayoi;Tabira, Takeshi
研究目的：衰老被认为会影响包括焦虑在内的情绪，草药yokukansan（YKS）用于治疗与老年性神经退行性疾病（如阿尔茨海默病）相关的情绪障碍，但其药理学特性尚未完全了解。本研究采用F344/N老年大鼠，观察YKS是否改善老年焦虑。材料与方法：给21月龄老龄大鼠灌胃益肝康3个月。检查年轻对照组（4月龄）、老年对照组（24月龄）和YKS治疗老年大鼠的自发活动，并通过计算自发活动测量期间和高架十字迷宫试验中的排泄物数量来评价这些动物的焦虑相关反应。采用微透析技术测定了前额叶皮层（PFC）细胞外5-羟色胺和多巴胺的浓度。此外，天冬氨酸氨基转移酶（AST），丙氨酸氨基转移酶（ALT），和氨（NH（3））在血浆中的浓度进行了测定。结果：虽然运动活动没有改变任何实验组之间，排泄的数量显着增加，老年大鼠相比，年轻的大鼠，这种增加显着改善YKS治疗。老年大鼠在高架十字迷宫开放臂的时间和频率也显着减少，这些减少显着改善YKS治疗。老年PFC的细胞外5-羟色胺和多巴胺的浓度显着下降：5-羟色胺增加超过年轻大鼠的水平和多巴胺部分改善YKS治疗，分别。结论：YKS对老年PFC中与年龄相关的焦虑有改善作用，并能增强PFC中多巴胺能和多巴胺能的传递，为老年焦虑症的治疗提供了重要的信息。此外，目前的数据部分证实了汉方的概念“肝病”。(C)2009爱思唯尔爱尔兰有限公司保留所有权利。
Aim of the study: Aging is thought to affect emotions including anxiety, and a herbal medicine, yokukansan (YKS), is used to treat emotional disturbances associated with age-related neurodegenerative disorders such as Alzheimer's disease, but its pharmacological properties have not been fully understood. The present study was designed to examine whether YKS improves age-related anxiety using F344/N aged rats. Moreover, the effects of YKS on liver function were examined.Materials and methods: YKS was administered to 21-month-old aged rats for 3 months. Locomotor activity of young control (4 months old), aged control (24 months old), and YKS-treated aged rats was examined, and the anxiety-related responses of these animals were evaluated by counting the number of excrements during locomotor activity measurement and in the elevated plus-maze test. The extracellular concentrations of serotonin and dopamine in the prefrontal cortex (PFC) were also measured using a microdialysis technique. Moreover, concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and ammonia (NH(3)) in plasma were measured.Results: Although locomotor activity did not change among any experimental groups, the number of excrements was significantly increased in aged rats compared to young rats, and this increase was significantly improved by YKS treatment. Aged rats also showed significant decreases in time and frequency in the open arm of the elevated plus-maze, and these decreases were significantly improved by YKS treatment. Extracellular concentrations of serotonin and dopamine in the aged PFC were significantly decreased: serotonin was increased over the level of young rats and dopamine was partially improved by YKS treatment, respectively. In addition, YKS improved age-related increase in NH3 concentration, but did not affect AST and ALT.Conclusions: YKS has improving activity for age-related increased anxiety and enhances serotonergic and dopaminergic transmissions in the aged PFC. These mechanisms provide information important for the treatment of anxiety in the elderly. Furthermore, the present data confirm partially the Kampo concept "liver disease". (C) 2009 Elsevier Ireland Ltd. All rights reserved.