Gender Differences in the Brain: Implications for the Study of Human Alcoholism

Abstract

Gender differences in alcohol intake and response to alcohol may be influenced by basic variations in the organization and modulation of male and female brains. Although a number of genetic, social, environmental, and metabolic factors have been proposed to explain the gender differences observed in risk for alcoholism, alcohol intake, and medical consequences of excessive alcohol intake, very little attention has been given to the role of gender differences in the brain regarding alcohol use. Recent evidence documents the influence of neurosteroids on neurotransmitter activity in the brain and the impact of alcohol on neurosteroid levels. Neurosteroids are found in different levels in males and females during development and throughout life, depending on factors such as age, stage of development, estrous and menstrual cycles, and stress. This study discusses the hypothesis that many of the gender differences observed concerning alcohol use and misuse are determined by gender differences in the brain, which in turn differentially influence the behavioral and neurochemical responses of males and females to alcohol.

Voluntary ethanol consumption in 22 inbred mouse strains

“…Female B6 mice had significantly greater intake of 6E, with a trend for an increase in 10E, when compared to their male counterparts. Nonetheless, these findings are consistent with clinical and preclinical studies documenting the existence of sex differences in sensitivity to a number of alcohol-related behaviors associated with neuroadaptation and reinforcement (e.g., Devaud et al, 2003;Finn et al, 2004aFinn et al, , 2004bGreen et al, 1999;Hashimoto and Wiren, 2007;Lancaster, 1995;Middaugh and Kelly, 1999;Rhodes et al, 2007;Vivian et al, 2001;Wiren et al 2006). …”

Sex-exclusive quantitative trait loci influences in alcohol-related phenotypes

“…These differences may arise from scalar effects, in which a locus is operational in both sexes, but with different effect sizes, or to nonscalar effects, in which the effects of loci in one sex are independent of the influence of the other sex [Neale and Cardon, 1992]. Such scalar effects underlie the identification of sex and gender differences found by Lancaster [1995] in alcohol-related processes. The nonscalar type of sex limitation is especially interesting in that reverse genetic studies of such loci could be fruitful in elucidating mechanisms underlying the differential expression of alcohol-related phenotypes in the two sexes.…”

“…88:647-652, 1999. © 1999 Wiley-Liss, Inc. KEY WORDS: QTL; sex specificity; nonscalar sex limitation INTRODUCTION Individual differences in alcohol-related phenotypes in humans have been attributed to ethnicity [Blane, 1993], cultural experiences [Barthwell, 1995;Westermeyer, 1995], age [Lindi et al, 1996;Rice et al, 1993], heredity [Lancaster, 1995], and socioeconomic status [Jones-Webb et al, 1995;Rossow and Amundsen, 1996], among other factors. Sex differences have also been well recognized in alcohol research, as illustrated by the work of Cloninger [1981], who proposed a typology of alcoholism in which Type I is more environmentsensitive and Type II has a substantial genetic component.…”

Animal models of the anxiogenic effects of ethanol withdrawal

“…Despite the fact that one-third of alcoholics in the US are women, and the growing evidence that males and females differ in their physiological and behavioral response to ethanol [Rivier, 1993;Blanchard and Glick, 1995;Lancaster, 1995], most ethanol studies have focused on male subjects and little information is available on sex differences in the anxiogenic effects of EW.…”