Effects of Toki-shakuyaku-san on electric footshock stress in ovariectomized mice

In the present study, ovariectomized mice were exposed to electric footshock stress for 7 days, and the duration of sodium pentobarbital-induced 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 the sham-operation group. After exposure to stress, however, the duration of sodium pentobarbital-induced sleep in ovariectomized mice was shortened significantly, compared to the ovariectomized mice without stress. When the effect of Toki-shakuyaku-san on the stress-induced shortening of sleep time was studied, it was found that the shortening of the sleep time was suppressed by treatment with Toki-shakuyaku-san. In ovariectomized mice, the increase in hypothalamic noradrenaline (NA) turnover in response to stress was significantly greater than that in mice with intact ovaries. The stress-induced enhancement of NA turnover was suppressed significantly by Toki-shakuyaku-san in a dose-dependent manner, beginning with a low dose level. When effect of 17Beta-estradiol on the stress induced-shortening of sleep time was examined in ovariectomized mice, by high doses of 17Beta-estradiol the shortening of the sleep time was prolonged. A major difference between 17Beta-estradiol and Toki-shakuyaku-san was the marked uterine weight gain observed following 17Beta-estradiol treatment despite no effect of Toki-shakuyaku-san on uterine weight. The results in this study suggest that Toki-shakuyaku-san may reduce menopausal symptoms by a mechanism different from that of estrogen.