Gender Differences in Blood Levels, But Not Brain Levels, of Ethanol in Rats

Abstract

Female rodents tend to drink more alcohol than males, a difference that emerges at puberty and appears to vary over the female estrous cycle. In addition, male and female rodents display different responses to alcohol; for example, female rats are reported to have faster elimination rates than males. We were interested in whether circulating ovarian hormones influence alcohol distribution to or elimination from the brain of rats, which might explain observed differences in drinking behavior. We administered 0.8 g/kg of ethanol via intraperitoneal injection to age-matched male and female Sprague-Dawley rats. Extracellular brain ethanol was sampled using microdialysis, and vascular ethanol concentrations were determined via tail blood collection, in two separate experiments. Ethanol pharmacokinetic parameters were calculated for both compartments. There were no differences in pharmacokinetic parameters due to gender or estrous cycle stage in brain ethanol concentration profiles. There were, however, differences in blood ethanol profiles: females showed faster elimination rates and a smaller area under the ethanol concentration versus time curve than males. In addition, the maximum concentration varied significantly across the estrous cycle. These results suggest that (1) circulating ovarian hormones do not influence alcohol distribution to the brain, but do influence distribution to more peripheral tissues such as the tail; and (2) apparent differences in tail blood alcohol levels may not reflect differences in brain levels.

Sex differences in adult Wistar rats in the voluntary consumption of ethanol after pre-exposure to ethanol-induced flavor avoidance learning

“…Perhaps the lower overall aversion index by the females in experiment 1 and the higher intake in the non pre-exposed females in experiment 2 could be explained by the slower rate of ethanol absorption in females, which would cause a delay in the adverse effects of the ethanol, allowing the females to drink more and for a longer period of time. However, while some studies did not obtain significant sex differences in the rate of ethanol elimination (Silveri and Spear, 2000), others have reported slightly faster ethanol clearance rates in females than males (Collins et al, 1975;Crippens et al, 1998). So, it does not appear that small differences in ethanol absorption between males and females would explain the differences in consumption found in our study.…”

Differences in the social consequences of ethanol emerge during the course of adolescence in rats: Social facilitation, social inhibition, and anxiolysis

“…In contrast, adolescent animals were found to be uniquely sensitive to facilitation of social interactions induced by low doses of ethanol under familiar test circumstances, social facilitation not evident at any dose under these circumstances in adult animals. No sex-related differences were found in sensitivity of adolescent and adult animals to ethanol-induced social facilitation, social inhibition, and anxiolysis, although sex differences in intake, pharmacokinetics, and some effects of ethanol have been reported in several studies (e.g., Blanchard & Glick, 1995;Cailhol & Morméde, 2001;Crippens et al, 1999;Lancaster, Brown, Coker, Elliott, & Wren, 1996;Robinson, Brunner, & Gonzales, 2002;Silveri & Spear, 1999;Tayyabkhan, Mammola, & Drugan, 2002;Webb, Burnett, & Walker, 2002).…”

Biological basis of sex differences in drug abuse: preclinical and clinical studies

“…One study examined the influence of ovarian hormones on the distribution to, and elimination of alcohol from the brain of female rats (Crippens et al 1999). The authors obtained brain and vascular ethanol concentrations through microdialysis, and blood collection via the tail bleed method, respectively.…”