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.

Corticotropin‐Releasing Factor Acting on Corticotropin‐Releasing Factor Receptor Type 1 is Critical for Binge Alcohol Drinking in Mice

“…This is in agreement with previous studies showing that female rodents consume greater amounts of alcohol and appear to be more sensitive to the effects of alcohol than males (Crippens et al, 1999; Lancaster and Spiegel, 1992; Middaugh et al, 1999; Peterson et al, 1991). This difference is most likely attributed to faster alcohol metabolism rates in female than male mice and rats (Crippens et al, 1999; Peterson et al, 1991). These findings may explain the discrepancy between alcohol intake and BECs between the sexes that we observed.…”

Exposure to nicotine during periadolescence or early adulthood alters aversive and physiological effects induced by ethanol

“…Changes in metabolic rates and volume distribution, however, were not directly assessed and, thus, cannot be ruled out. Furthermore, blood alcohol levels do not necessarily correspond to, and are generally lower than, brain alcohol levels (Crippens et al , 1999, Robinson et al , 2002, Smolen and Smolen, 1989). Additionally, nicotine pretreatment is capable of reducing brain and cerebrospinal fluid concentrations of alcohol which could potentially reduce the aversive effects of alcohol (Hisaoka and Levy, 1985).…”

Sex Differences in Ethanol Intake and Sensitivity to Aversive Effects during Adolescence and Adulthood

“…Another potential explanation for the lack of sex differences in BECs could be due to differences in ethanol elimination or absorption. 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 , 1999). …”