Yanagida Satoru, Motomura Keisuke, Ohashi Ayako, Hiraoka Kentaro, Miura Tomofumi, Kanba Shigenobu
Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Neurosci Lett. 2016 Aug 26;629:119-124. doi: 10.1016/j.neulet.2016.06.059. Epub 2016 Jul 1.
The forced swim test (FST) has been widely used for the preclinical evaluation of antidepressant drugs. Despite considerable differences in the protocol, equivalence of the FST for rats and mice has been rarely questioned. Previous research on the FST for rats revealed that repeated administration of antidepressant drugs attenuates the c-Fos response to swim stress in the hypothalamus and limbic regions. However, few studies have made similar investigations using the FST for mice. In the present study, we explored the mouse brain through immunohistochemistry staining for c-Fos after acute administration of imipramine or saline with or without a subsequent swim session. Imipramine enhanced the c-Fos density in regions of the central extended amygdala, while forced swim stress increased c-Fos expression in some hypothalamic (the ventrolateral preoptic nucleus and dorsomedial nucleus) and brain stem regions, which is consistent with previous reports. In contrast to previous literature with rats, swim stress brought a significant increase in c-Fos expression in the lateral septal nucleus and some other regions in the hypothalamus (the intermediate hypothalamic area, the paraventricular and arcuate nucleus) only in the imipramine-pretreated group, which has not been observed previously. In the arcuate nucleus, double immunostaining revealed that c-Fos was rarely co-expressed with proopiomelanocortin or tyrosine hydroxylase regardless of imipramine treatment. The present results suggest that the activation of several regions in the lateral septum and the hypothalamus underlies antidepressant-like effect in the mouse FST.
强迫游泳试验（FST）已被广泛用于抗抑郁药物的临床前评估。尽管实验方案存在相当大的差异，但大鼠和小鼠FST的等效性很少受到质疑。先前对大鼠FST的研究表明，重复给予抗抑郁药物可减弱下丘脑和边缘区域对游泳应激的c-Fos反应。然而，很少有研究使用小鼠FST进行类似的研究。在本研究中，我们通过免疫组织化学染色检测c-Fos，对给予丙咪嗪或生理盐水后急性给药且有或无后续游泳环节的小鼠脑进行了探索。丙咪嗪增强了中央杏仁核扩展区域的c-Fos密度，而强迫游泳应激增加了一些下丘脑（腹外侧视前核和背内侧核）和脑干区域的c-Fos表达，这与先前的报道一致。与先前关于大鼠的文献不同，游泳应激仅在丙咪嗪预处理组中使外侧隔核和下丘脑其他一些区域（下丘脑中间区域、室旁核和弓状核）的c-Fos表达显著增加，这在之前尚未观察到。在弓状核中，双重免疫染色显示，无论丙咪嗪治疗如何，c-Fos很少与阿片促黑激素原或酪氨酸羟化酶共表达。目前的结果表明，外侧隔核和下丘脑的几个区域的激活是小鼠FST中抗抑郁样作用的基础。
