Alcohol absorption rate affects hypothermic response in mice: evidence for rapid tolerance

Three studies were conducted to examine how absorption rate affects rapid tolerance to ethanol-induced hypothermia. Two procedures for administering alcohol were used to vary the rates of ethanol absorption: a 40-min intravenous (IV) infusion and the more rapidly absorbed intraperitoneal (IP) injection. Hypothermic responses of Long-Sleep (LS), Short-Sleep (SS), and DBA/2JIbg (DBA) mice were examined. Although IV ethanol infusions produced similar or higher blood ethanol levels (BELs) compared to IP administration, the degree of hypothermia was significantly greater with the more rapidly absorbed IP administration. It was concluded that the rate at which ethanol increases in the blood influences the degree of hypothermia: the greater the rate of blood ethanol increase, the greater the hypothermic effect. Rapid development of tolerance to ethanol may explain why a slow increase in BEL produces less hypothermia than a rapid increase in BEL. The IV route provides a precise method of drug administration for the study of acute tolerance.