Effects of adolescent alcohol exposure via oral gavage on adult alcohol drinking and co-use of alcohol and nicotine in Sprague Dawley rats

Background: Preclinical models simulating adolescent substance use leading to increased vulnerability for substance use disorders in adulthood are needed. Here, we utilized a model of alcohol and nicotine co-use to assess adult addiction vulnerability following adolescent alcohol exposure. Methods: In Experiment 1, adolescent (PND30) male and female Sprague-Dawley rats received 25% ethanol (EtOH) or a control solution via oral gavage every 8 h, for 2 days. In young adulthood, animals were tested with a 2-bottle choice between H20% and 15% EtOH or 0.2% saccharin/15% EtOH, followed by co-use of oral Sacc/EtOH and operant-based i.v. nicotine (0.03 mg/kg/infusion) self-administration. In Experiment 2, adolescents received control gavage, EtOH gavage, or no-gavage, and were tested in young adulthood in a 2-bottle choice between H20% and 15% EtOH, Sacc/EtOH, or 0.2% saccharin. Results: In Experiment 1, the adolescent EtOH gavage reduced adult EtOH consumption in the 2-bottle choice, but not during the co-use phase. During co-use, Sacc/EtOH served as an economic substitute for nicotine. In Experiment 2, the control gavage increased adult EtOH drinking relative to the no-gavage control group, an effect that was mitigated in the EtOH gavage group. In both experiments, treatment group differences in EtOH consumption were largely driven by males. Conclusions: EtOH administration via oral gavage in adolescence decreased EtOH consumption in adulthood without affecting EtOH and nicotine co-use. Inclusion of a no-gavage control in Experiment 2 revealed that the gavage procedure increased adult EtOH intake and that including EtOH in the gavage buffered against the effect.