Section of Oriental Medicine, Department of Geriatric Medicine, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology (NCGG), 36-3 Gengo, Morioka, Obu, Aichi 474-8511, Japan.
J Ethnopharmacol. 2013 Aug 26;149(1):93-102. doi: 10.1016/j.jep.2013.06.005. Epub 2013 Jun 12.
A traditional Japanese (Kampo) medicine, yokukansan, has long been used to treat neurosis, insomnia, and night crying and irritability in children. Recently, this medicine has reported to improve the behavioral and psychological symptoms of dementia that often become problematic in patients with Alzheimer's disease and other forms of dementia.
Several animal studies have reported that yokukansan has an anxiolytic effect. However, the underlying mechanisms are not yet understood. In the present study, we investigated the effects in rats of single and repeated administrations of yokukansan on anxiety-like behaviors, stress responses, and the brain regions involved.
Yokukansan dissolved in water (100 or 300 mg/kg) was administered orally to F344/N male rats 1h before each test or for two weeks before the tests began. Locomotor activity and anxiety-related behavior in the open-field test and the elevated plus-maze test, serum corticosterone levels, and restraint stress-induced c-Fos expression in various brain regions as a marker of neuronal activation were evaluated in both the vehicle-treated and yokukansan-treated rats.
A single administration of yokukansan had no effect on locomotor activity or anxiety-like behavior; however, repeated administration decreased anxiety-like behavior in a dose-dependent manner. Neither single nor repeated administration of yokukansan had an effect on the basal or stress-induced levels of serum corticosterone. For c-Fos expression, restraint stress increased the number of c-Fos-positive cells in the subdivisions of the prefrontal cortex, amygdala, and hypothalamus. Repeated administration of yokukansan decreased the stress-induced c-Fos expression in the prelimbic cortex and the basolateral and medial amygdaloid nuclei.
The present study indicates that repeated oral administration of yokukansan has an anxiolytic effect and that this effect may be associated with attenuated neuronal activity in the medial prefrontal cortex and amygdala.
一种传统的日本（汉方药）药物，优克安神，长期以来一直用于治疗神经症、失眠、儿童夜间哭闹和烦躁。最近，这种药物被报道可以改善阿尔茨海默病和其他形式痴呆症患者经常出现的行为和心理症状的痴呆症。
几项动物研究报告称，优克安神具有抗焦虑作用。然而，其潜在机制尚不清楚。在本研究中，我们研究了单次和重复给予优克安神对焦虑样行为、应激反应以及涉及的大脑区域的影响。
将优克安神溶解在水中（100 或 300mg/kg），在每次测试前 1 小时或在测试开始前两周内口服给予 F344/N 雄性大鼠。在开放场测试和高架十字迷宫测试中评估运动活动和焦虑样行为、血清皮质酮水平以及作为神经元激活标志物的束缚应激诱导的 c-Fos 表达，在给予和未给予优克安神的大鼠中进行评估。
单次给予优克安神对运动活动或焦虑样行为没有影响；然而，重复给药以剂量依赖性方式降低焦虑样行为。单次或重复给予优克安神对基础或应激诱导的血清皮质酮水平均没有影响。对于 c-Fos 表达，束缚应激增加了前额皮质、杏仁核和下丘脑各亚区的 c-Fos 阳性细胞数量。重复给予优克安神可减少应激诱导的前扣带皮层和外侧和内侧杏仁核核的 c-Fos 表达。
本研究表明，重复口服给予优克安神具有抗焦虑作用，这种作用可能与内侧前额皮质和杏仁核神经元活性降低有关。
