Suzuki T, Koike Y, Yoshii T, Yanaura S
Yakubutsu Seishin Kodo. 1986 Dec;6(4):373-80.
Sex differences in physical dependence on barbital (BAR), which is not readily metabolized in rats, were studied by the drug-admixed food method. The concentration of BAR in the food was gradually increased from 1 and 2 up to 6 and 8 mg/g food concurrently available to each rat over a period of 36 days in both male and female Sprague-Dawley rats. Sedation and muscle relaxation were observed in males at the 4 and 6 mg/g condition and to a greater degree at 6 and 8 mg/g of food. This effect was seen only at the highest drug concentration, 6 and 8 mg/g food, in females. Physical dependence was assessed in both sexes after substitution of normal food for the BAR-admixed food. Various signs of BAR withdrawal were observed including vocalization, irritability, muscle rigidity, tremors and convulsions. The incidence of convulsions was 76.9% in females and 45.5% in males, respectively. Maximum weight loss was 15.4% in females and 12.1% in males. However, brain BAR concentrations in the male rats were higher than that in the female rats 9 hours before onset of withdrawal and at all later time points tested. Thus, we have demonstrated that weak sex differences in physical dependence on BAR exist and suggest that this difference resulted from a difference in CNS sensitivity to BAR.
采用药物混合食物法，对大鼠体内不易代谢的巴比妥（BAR）身体依赖性的性别差异进行了研究。在36天的时间里，同时向雄性和雌性斯普拉格-道利大鼠提供食物中BAR浓度逐渐增加的食物，从1和2毫克/克逐渐增加到6和8毫克/克。在食物中BAR浓度为4和6毫克/克时，雄性大鼠出现镇静和肌肉松弛，在食物中BAR浓度为6和8毫克/克时，这种效应更为明显。而在雌性大鼠中，只有在食物中BAR浓度最高，即6和8毫克/克时，才观察到这种效应。在用正常食物替代含BAR的食物后，对两性的身体依赖性进行了评估。观察到了各种BAR戒断症状，包括鸣叫、易怒、肌肉僵硬、震颤和惊厥。惊厥发生率在雌性大鼠中为76.9%，在雄性大鼠中为45.5%。最大体重减轻在雌性大鼠中为15.4%，在雄性大鼠中为12.1%。然而，在戒断开始前9小时以及之后所有测试时间点，雄性大鼠脑内BAR浓度均高于雌性大鼠。因此，我们证明了在对BAR的身体依赖性方面存在微弱的性别差异，并表明这种差异是由中枢神经系统对BAR的敏感性差异所致。
