Hayase T, Yamamoto Y, Yamamoto K, Fukui Y
Department of Legal Medicine, Kyoto University, Japan.
Nihon Arukoru Yakubutsu Igakkai Zasshi. 1996 Feb;31(1):95-109.
The purpose of this study was to examine the lethal effects of combining cocaine with ethanol in mice by assaying for cocaethylene at the time of death. After the voluntary oral ingestion of ethanol in the form of a liquid diet containing 35% ethanol-derived calories for 5 days, intraperitoneal cocaine (60 mg/kg) was administered daily for up to 5 days while the ethanol diet continued (ethanol diet group). The mice in the ethanol diet group were paired with control mice that received a control liquid diet containing equivalent carbohydrate calories in the form of sucrose instead of ethanol (control diet group). In order to analyze the drugs, samples (blood, liver and brain) were collected for both groups from the dead animals that could not tolerate the 5 days of cocaine administration. A higher rate of lethality was observed in the ethanol diet group as compared to the control diet group. Furthermore, various patterns of cocaine lethality were revealed under different conditions of ethanol intake. According to the survival times after the last cocaine administration, observed respiratory and locomotive disorders, and drug concentrations, a total of 5 subgroups in the ethanol diet group (Groups E1-E5) and a total of 3 subgroups in the control diet group (Groups C1-C3) were differentiated. The ratio of the mean cocaethylene concentration relative to the mean cocaine concentration was over 30% in the livers of animals in an earliest lethal subgroup (Group E1). In addition, examination of all of the dead animals in the ethanol diet group revealed the prolonged presence of cocaethylene in the brain of the mice that died within 2 hours. Thus, it was suggested that cocaethylene has strong effects on the brain receptors and influences cocaine lethality.
本研究的目的是通过在死亡时检测可卡因乙烯酯，来研究可卡因与乙醇联合使用对小鼠的致死作用。以含35%乙醇热量的液体饲料形式让小鼠自愿口服乙醇5天，之后每天腹腔注射可卡因（60毫克/千克），持续5天，同时继续给予乙醇饲料（乙醇饲料组）。乙醇饲料组的小鼠与接受含等量碳水化合物热量的蔗糖而非乙醇的对照液体饲料的对照小鼠配对（对照饲料组）。为了分析药物，从无法耐受5天可卡因注射的死亡动物身上采集两组的样本（血液、肝脏和大脑）。与对照饲料组相比，乙醇饲料组观察到更高的致死率。此外，在不同乙醇摄入条件下揭示了可卡因致死的各种模式。根据最后一次注射可卡因后的存活时间、观察到的呼吸和运动障碍以及药物浓度，乙醇饲料组共分为5个亚组（E1 - E5组），对照饲料组共分为3个亚组（C1 - C3组）。在最早死亡的亚组（E1组）动物的肝脏中，可卡因乙烯酯平均浓度与可卡因平均浓度之比超过30%。此外，对乙醇饲料组所有死亡动物的检查发现，在2小时内死亡的小鼠大脑中可卡因乙烯酯存在时间延长。因此，提示可卡因乙烯酯对脑受体有强烈作用并影响可卡因的致死性。
