EFFECTS OF TOKI-SHAKUYAKU-SAN ON ELECTRIC FOOTSHOCK STRESS IN OVARIECTOMIZED MICE

In the present study, ovariectomized mice were exposed to electric foo tshock stress for 7 days, and the duration of sodium pentobarbital-ind uced sleep was measured on the day following the last stress exposure. In ovariectomized mice, the duration of sodium pentobarbital-induced sleep before exposure to stress did not differ markedly from that in t he sham-operation group. After exposure to stress, however, the durati on of sodium pentobarbital-induced sleep in ovariectomized mice was sh ortened significantly, compared to the ovariectomized mice without str ess. When the effect of Toki-shakuyaku-san on the stress-induced short ening of sleep time was studied, it was found that the shortening of t he sleep time was suppressed by treatment with Toki-shakuyaku-san. In ovariectomized mice, the increase in hypothalamic noradrenaline (NA) t urnover in response to stress was significantly greater than that in m ice with intact ovaries. The stress-induced enhancement of NA turnover was suppressed significantly by Toki-shakuyaku-san in a dose-dependen t manner, beginning with a low dose level. When the effect of 17 beta- estradiol on the stress induced-shortening of sleep time was examined in ovariectomized mice, by high dose of 17 beta-estradiol the shorteni ng of the sleep time was prolonged. A major difference between 17 beta -estradiol and Toki-shakuyaku-san was the marked uterine weight gain o bserved following 17 beta-estradiol treatment despite no effect of Tok i-shakuyaku-san on uterine weight. The results in this study suggest t hat Toki-shakuyaku-san may reduce menopausal symptoms by a mechanism d ifferent from that of estrogen.