Gonadal Sex and Sex-Chromosome Complement Interact to Affect Ethanol Consumption in Adolescent Four Core Genotypes Mice

BackgroundSex differences in ethanol consumption have been reported in both humans and laboratory rodents, but the independent/dependent contributions of genetic and hormonal sex{square}biasing mechanisms to these phenotypes have not yet been fully explored. MethodsTo examine the contributions of sex-chromosome complement (SCC) and gonadal sex (GS) to ethanol consumption, we studied adolescent (28-32 days old) four core genotypes (FCG) mice (C57BL/6J background; FCG model allows for independent assortment of GS and SCC) using a modified drinking-in-the-dark (DID) procedure. Mice were offered concurrent access to 20%, 10% and 0% ethanol (in water) in four daily 2-hour sessions. Consumption at the level of individual bouts was recorded. ResultsAlthough all four genotype groups preferred the 20% ethanol over 10% and 0%, and showed similar consumption of the 10% and 0% solutions, the group rankings for consumption of the 20% ethanol solution were XX+testes > XY+testes > XY+ovaries > XX+ovaries. Thus, an interaction was observed between SCC and GS for which the simple effect of SCC was greatest in mice with ovaries (XY > XX) and the simple effect of GS was greatest in XX mice (testes > ovaries). Moreover, these effects varied in magnitude across and within drinking sessions. The behavioral microstructure of ethanol consumption (i.e., parameterization of within-session discriminable drinking bouts) support the validity of our 3-bottle modification of the DID procedure as a model of binge-like consumption as: (1) the consumption rate of the 20% ethanol solution was ~80 g EtOH/kg/h within a bout (~12 s/bout, ~3 bouts/session), (2) most of this ethanol consumption was completed in a single bout and (3) within-session ethanol consumption was greater earlier than later, indicating "front loading." ConclusionsThese results indicate that SCC and GS interact on ethanol consumption in adolescent FCG mice on a C57BL/6J background to affect binge-like consumption from the very initiation of access and that these effects are dynamic as they varied both across and within sessions. HighlightsO_LIGonadal sex and sex-chromosome complement interact on ethanol consumption in adolescent four core genotypes mice C_LIO_LIIn adolescent four core genotypes mice, mice with testes drink more ethanol than mice with ovaries, particularly in the presence of an XX karyotype C_LIO_LIIn adolescent four core genotypes mice, XY mice drink more ethanol than XX mice, but only in mice with ovaries C_LIO_LIThe effects of sex-biasing biological factors on the patterns of ethanol consumption by adolescent four core genotypes mice that we observed in our 3-bottle Drinking-in-the-Dark procedure showed face validity with some of the sex/gender differences observed in human adolescents C_LI