Assessment of Cocaethylene Lethality in Long–Evans Female and Male Rats

Cocaethylene, the metabolite of cocaine produced only in the presence of alcohol, produces a number of pharmacological, physiological, and behavioral effects. It also has a range of toxicological consequences, the most severe being lethality. Given that the assessments of cocaethylene lethality have...

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Bibliographic Details
Published in:Neurotoxicology and teratology 1998-07, Vol.20 (4), p.459-463
Main Authors: Sobel, B.-F.X., Hutchinson, A.C., Diamond, H.F., Etkind, S.A., Ziervogel, S.D., Ferrari, C.M., Riley, A.L.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cocaethylene
Cocaine - analogs & derivatives
Cocaine - toxicity
Drug addictions
Drug Evaluation, Preclinical
Evaluation Studies as Topic
Female
Injections, Intraperitoneal
Lethal Dose 50
Lethality
Male
Medical sciences
Rats
Rats, Long-Evans
Sex Characteristics
Sex differences
Toxicology
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Summary:Cocaethylene, the metabolite of cocaine produced only in the presence of alcohol, produces a number of pharmacological, physiological, and behavioral effects. It also has a range of toxicological consequences, the most severe being lethality. Given that the assessments of cocaethylene lethality have been limited to mice, the present study assessed the lethality of cocaethylene in rats. Further, because of within-species sex differences with its parent compound, cocaine, cocaethylene lethality was also examined in both females and males. Specifically, female and male rats were injected IP with 75, 87, 100, 115, and 133 mg/kg cocaethylene and observed over a 24-h period. Deaths were dose dependent and occurred within 30 min for both females and males. For females, the LD 50 was 96 mg/kg; for males, the LD 50 was 70 mg/kg. The percentage of rats displaying severe effects (i.e., seizure and death) increased with dose across all postinjection times. Further, these effects occurred earlier as dose increased. Differences in the LD 50 for rats and mice, as well as the greater sensitivity to cocaethylene in male rats, are discussed.
ISSN:0892-0362
1872-9738
DOI:10.1016/S0892-0362(97)00132-3