Role of brain cocaethylene levels in combined cocaine-ethanol lethality in mice.
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.
Hayase
T
T
Department of Legal Medicine, Kyoto University, Japan.
Yamamoto
Y
Y
Yamamoto
K
K
Fukui
Y
Y
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis / Q000633:toxicity*; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR
D000431:Ethanol; C066444:cocaethylene; D003042:Cocaine