Yutrzenka G J, Patrick G A, Rosenberger W
J Pharmacol Exp Ther. 1985 Jan;232(1):111-8.
The i.p. administration of pentobarbital using an escalating drug-dose schedule for an 11-day period resulted in the establishment of dependence on pentobarbital in male rats. Mean plasma pentobarbital levels were approximately 5 micrograms/ml during the first 3 days of the infusion period. Subsequently, there was observed a dose-responsive increase in plasma pentobarbital levels for the next 5 days, with a decline in pentobarbital levels noted during the final 3 days of the pentobarbital infusion period. Removal of pentobarbital from the infusate resulted in a rapid decline in plasma levels to less than 50% by 8 hr into the drug-free period and to barely detectable levels by 24 hr. This was correlated with a steadily increasing occurrence of withdrawal signs, with a peak occurrence by 7 to 9 hr after initiation of the drug-free period. Spontaneous locomotor activity was significantly greater in pentobarbital-dosed animals during withdrawal than in saline-infused control rats. The i.p. infusion of pentobarbital is a quick and reliable method for the study of barbiturate dependence in the rat.
在11天的时间里，采用递增药物剂量方案腹腔注射戊巴比妥，导致雄性大鼠对戊巴比妥产生依赖性。在输注期的前3天，血浆戊巴比妥平均水平约为5微克/毫升。随后，在接下来的5天里观察到血浆戊巴比妥水平呈剂量反应性增加，在戊巴比妥输注期的最后3天观察到戊巴比妥水平下降。从输注液中去除戊巴比妥后，血浆水平在无药期开始8小时内迅速下降至低于50%，到24小时时降至几乎检测不到的水平。这与戒断症状的发生率稳步增加相关，在无药期开始后7至9小时出现峰值。在戒断期间，腹腔注射戊巴比妥的动物的自发运动活性明显高于注射生理盐水的对照大鼠。腹腔注射戊巴比妥是研究大鼠巴比妥类药物依赖性的一种快速可靠的方法。
