Key result
Sex chromosome complement and gonadal sex interact to drive ethanol consumption differences in adolescent mice.
Why the study?
Sex differences in ethanol consumption have been reported, but the independent and dependent contributions of genetic and hormonal sex biasing mechanisms remain incompletely explored.
Gonadal sex and sex-chromosome complement interact to affect binge-like ethanol consumption in adolescent mice, with gonadal sex effects most pronounced in XX mice.
Sex chromosome-gonadal interactions shape adolescent ethanol intake in mice; leaves open human translation and requires prospective studies.
Background/Objectives: Sex differences in ethanol consumption have been reported in both humans and laboratory rodents, but the independent/dependent contributions of genetic and hormonal sex biasing mechanisms to these phenotypes have not yet been fully explored. Methods: To 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 on a C57BL/6J background, a model which allows for independent assortment of GS and SCC. A modified drinking-in-the-dark (DID) procedure was employed, in which mice were offered concurrent access to 20%, 10% and 0% ethanol (in water) in four daily 2 h sessions. Consumption at the level of individual bouts was recorded. Results: Overall ethanol intake differed substantially by group and was driven almost entirely by differences in consumption of the 20% ethanol solution; all groups preferred the 20% solution over the 10% and 0% solutions, but consumed similar amounts of the 10% and 0% solutions. Intake of the 20% ethanol solution followed the rank order XXM > XYM > XYF > XXF. This pattern reflects an interaction between SCC and GS, such that SCC effects were greatest in gonadal females (XY > XX), whereas GS effects were greatest in XX mice (gonadal males > gonadal females). Moreover, the magnitude of these effects varied both 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 three-bottle modification of the DID procedure as a model of binge-like consumption, because (1) the consumption rate of the 20% ethanol solution was ~80 g EtOH/kg/h within a bout (~12 s/bout, ~three 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.” Conclusions: These results suggest that the effects of GS on binge-like ethanol consumption are observed in early adolescence and moderated by SCC in adolescent FCG mice, with GS effects most pronounced in XX mice and SCC effects evident mainly in gonadal females.
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Jentsch et al. (2026) studied Ethanol consumption. Sex-chromosome complement and gonadal sex vs. Different combinations (XXM, XYM, XYF, XXF) was evaluated on Ethanol consumption (intake of 20% ethanol solution). In adolescent mice, intake of 20% ethanol followed the rank order XXM > XYM > XYF > XXF, reflecting an interaction between sex-chromosome complement and gonadal sex.
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