ヨヒンビン投与卵巣摘出ラットにおけるホットフラッシュ様症状に対するエストロゲン及び桂枝茯苓丸の作用
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Hot flash (HF) is the most common phenomenon in climacteric symptoms which often develop concomitantly with a decrease in estrogen in postmenopausal women. The onset mechanism of the hot flash is complicated and remains unclear. To date, some animal models of postmenopausal HF have been devised, but they are not fully available because of the difficulty in producing them. It is thought that hyperactivity of the central α-adrenergic system with a decrease in estrogen participates in the onset of postmenopausal HF. Therefore, in the present study, we examined whether a HF model could be easily produced by administering yohimbine (YOH), a presynaptic α2-adrenoceptor antagonist which promotes norepinephrine release, to female rats. HF-like symptoms such as a rise in tail skin temperature and a fall in rectal temperature were shown in the rats who received YOH (3 mg/kg) subcutaneously seven days after the ovariectomy (OVX). Such symptoms following YOH administration were observed in sham rats as well, but were much more clearly noted in OVX rats. We next examined the effects of various drugs, which are clinically effective against postmenopausal HF, on HF-like symptoms in YOH-treated OVX rats: clonidine, a presynaptic α2-adrenoceptor agonist which inhibits norepinephrine release; β-estradiol as an estrogen; and Keishibukuryogan, a Kampo medicine. These drugs inhibited HF-like symptoms in YOH-treated OVX rats. These results suggest that the activity of the α-adrenergic system is enhanced with a decrease in estrogen in OVX rats whereby YOH causes HF-like symptoms more conspicuously than in sham rats. Therefore, it is thought that YOH-treated OVX rats will be a novel and simple model of postmenopausal HF.
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