Tolerance to effects of high doses of ethanol: 1. Lethal effects in mice

Pharmacol Biochem Behav. 1993 Jun;45(2):465-72. doi: 10.1016/0091-3057(93)90266-v.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Drug Tolerance / physiology
  • Ethanol / administration & dosage
  • Ethanol / toxicity*
  • Lethal Dose 50
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Species Specificity
  • Time Factors

Substances

  • Ethanol