This study describes the development and characterization of a binge drinking model in which a single dose of ethanol (EtOH) is administered by gavage to B6C3F1 mice. Blood EtOH levels were monitored over time after administration of EtOH at doses of 3.0-7.0 g/kg. Peak levels were in the range of 0.2-0.5%, and clearance was complete within 2-12 hr. Substantial increases in blood corticosterone levels were noted. Behavioral changes in EtOH-treated mice aged 8 weeks ranged from no effect (3-4 g/kg) to severe ataxia (6-7 g/kg). In mice aged 16 weeks, a dosage of 7 g/kg caused less of the righting reflex in some animals and severe ataxia in most of the others. Clinical chemistry results did not indicate biologically important changes in general physiological/homeostatic systems in EtOH-treated mice, but there were indications of minor liver damage at the 7 g/kg dosage. Thus, administration of EtOH to B6C3F1 mice by gavage produces behavioral changes, changes in blood EtOH levels, and probably glucocorticoid levels representative of at least some human binge drinkers. The model was used to evaluate the effects of binge drinking on antibody responses, and the results indicate the model will be useful for such studies.

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Previous studies demonstrate that the effects of one chemical stressor on selected immunological parameters can be predicted on the basis of the area under the corticosterone concentration vs. time curve. However, it is not clear if this is applicable to other chemical stressors. The present study was conducted to determine if the stress-induced immunological effects of atrazine and ethanol could be predicted, and if it is feasible to use one immunological parameter as a biomarker of stress to predict the quantity of changes expected in other immunological parameters. The area under the corticosterone concentration-versus-time curve (AUC) was measured in mice treated with ethanol (EtOH, 4, 5, 6, or 7 g/kg by oral gavage) or atrazine (ATZ, 100, 200, or 300 mg/kg, ip). The effects of the same dosages of these chemicals on thymus and spleen cellularity, lymphocyte subpopulations in the thymus and spleen, expression of MHC class II protein on splenocytes, antibody responses to keyhole limpet hemocyanin, and natural killer-cell activity were determined. Models were derived describing the relationship between corticosterone AUC and immunological changes induced by these chemicals. The results for these chemical stressors were more similar to results obtained from mice subjected to restraint stress than from mice treated with exogenous corticosterone. Some effects were greater than predicted on the basis of the stress response alone, indicating other mechanisms of immunotoxicity. One of the parameters (MHC class II expression) was evaluated as a predictive biomarker for stress-related immunosuppression, and the results suggest it could be suitable for that purpose.

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