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 wer e two windows with very low density of probability of death between 30 -130 min and between 22-25 h following lethal injections. This time st ructure of the probability density function did not significantly depe nd 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 m ore sensitive to ethanol-induced lethality (LD50 = 6.6 g/kg) and over 99% of deaths occurred between 5-200 min following injections of the d oses 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 follo wing 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 etha nol, 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. T he results suggest that: a) Ethanol-induced lethality is not a unitary phenomenon and that deaths thta occurred within distinct waves probab ly have different causes; b) mice strains have different susceptibilit y to different causes of ethanol-induced deaths; c) preexposure to 3.5 g/kg ethanol results in significant but small increase in tolerance t o ethanol-induced lethality.