Tolerance to effects of high doses of ethanol: 1. Lethal effects in mice.
Male Swiss Webster mice were injected with ethanol doses ranging from 6.5-10.5 g/kg (20% w/v, IP). Survival time distribution revealed three waves of deaths with peaks around 5 min, 300 min, and 33 h. There were two windows with very low density of probability of death between 30-130 min and between 22-25 h following lethal injections. This time structure of the probability density function did not significantly depend upon ethanol overdose, novelty of the experimental environment, or prior injections of saline and/or 3.5 g/kg ethanol. Injections of high doses of ethanol in BALB/c mice showed that this strain of mice was more sensitive to ethanol-induced lethality (LD50 = 6.6 g/kg) and over 99% of deaths occurred between 5-200 min following injections of the doses from 5.5-7.5 g/kg. Preexposure to ethanol increased tolerance to ethanol-induced lethality. LD50 increased from 8.1 g/kg (at 24 h following lethal injections in ethanol-naive Swiss Webster mice) to 8.5 and 9.0 g/kg in mice following four and eight injections of 3.5 g/kg ethanol, respectively. In BALB/c mice, eight prior injections of 3.5 g/kg ethanol increased LD50 also slightly but significantly to 7.15 g/kg. The results suggest that: a) Ethanol-induced lethality is not a unitary phenomenon and that deaths that occurred within distinct waves probably have different causes; b) mice strains have different susceptibility to different causes of ethanol-induced deaths; c) preexposure to 3.5 g/kg ethanol results in significant but small increase in tolerance to ethanol-induced lethality.
Tsibulsky
V L
VL
Department of Psychology, Concordia University, Montreal, Quebec, Canada.
Amit
Z
Z
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013045:Species Specificity; D013997:Time Factors
D000431:Ethanol