Sex differences in ethanol-induced hypnosis and hypothermia in young Long-Evans rats

Introduction: Females experience greater liver damage, have reduced brain size, and have greater memory deficits than do males with a similar history of alcoholism. Females have higher peak alcohol levels and faster elimination rates than males. Our goal was to study sex differences in the response of young ethanol-naive outbred Long-Evans rats to acute ethanol exposure so that we may better understand why females are more sensitive to alcohol toxicity than males. Methods: Females aged 49 days and males aged 43 days, weighing 153.6 and 177.5 g, respectively, were tested for their initial response to ethanol. Fasted (12 hr) females (in diestrous) and males were given an intraperitoneal injection of 3.0 g/kg of ethanol (v/v in 0.9% sterile saline). Body temperature, loss of the righting reflex (LORR), return of the righting reflex, and tail blood alcohol concentration (BAC) were monitored. Results: LORR occurred at the same time in females and males. The return of the righting reflex occurred later in males than in females. BACs were the same in the males and females except at LORR, when BAC was lower in the males. Acute ethanol tolerance developed in more males than females. Females demonstrated a slower recovery from peak ethanol-induced hypothermia than males. The proportions of lean body mass, ethanol elimination, and ethanol metabolism were similar in the females and males. Conclusions: Ethanol-naive young male and female Long-Evans rats demonstrated sex differences in their initial responses to ethanol. Males were more sensitive than females to the hypnotic effect of ethanol, whereas females were more sensitive than males to ethanol-induced hypothermia. In addition, more males than females developed acute ethanol tolerance. Investigating the mechanisms underlying these differences may help us to understand why females experience more of the adverse effects of alcohol consumption than males.