Age effects on chronic tolerance to ethanol hypnosis and hypothermia

Male Fischer 344 rats of three different ages (young, 4 months; middle, 13 months; and old, 25 months) were tested for their hypnotic and hypothermic response to a 3.5 g/kg dose of ethanol on day 1 and after an 8-day exposure to 4.0 g/kg of ethanol administered via intragastric intubation. All three age groups displayed, to a similar extent, an increased rate of blood ethanol disappearance (metabolic tolerance) on day 10 and day 16, as compared to day 1. Both young and middle-age rats demonstrated tolerance to ethanol hypothermia, but older rats did not. The same test dose of ethanol (3.5 g/kg, IP) administered on day 16, after a 5-day interval with no ethanol, produced a hypnosis response similar to that observed on day 1 (no tolerance), but the response to ethanol hypothermia was still significantly reduced over the day 1 and day 10 value in young and middle-age rats, suggesting a persistence and intensification of tolerance to hypothermia over the 5-day rest interval. However, tolerance to ethanol hypothermia was not observed in old rats. Thus, the effects of age on the development of chronic functional tolerance were complex and depended upon the test measure used.