A mixed model of adolescent alcohol exposure reveals divergent behavioral and neural outcomes.

Across one's lifetime, heavy alcohol use during adolescence confers the highest risk for developing an alcohol use disorder (AUD), and therefore understanding its impact on the adolescent brain is essential for advancing effective interventions. Preclinical models are critical for investigations into the long-term neurobiological consequences of adolescent alcohol exposure with current mouse paradigms capturing either modest alcohol levels through voluntary consumption or high alcohol levels through passive exposure methods. The current study investigates the outcome of a mixed model of adolescent alcohol exposure by combining volitional adolescent alcohol intake using 2-bottle choice interleaved with alcohol vapor exposure. Our results show that 2 cycles of alcohol vapor elevate alcohol consumption and compulsive-like drinking behavior when measured in late adolescence, without affecting adult alcohol consumption. Neural activation patterns measured through c-Fos expression following adult alcohol consumption demonstrated that adolescent alcohol vapor exposed mice had increased activity in NAc core and CeA, with sex-dependent effects seen in PFC activation. We conclude that mixed alcohol consumption and vapor paradigms have short-term behavioral consequences and long-term neural effects.