A substantial percentage of pregnant smokers stop using traditional cigarettes and switch to alternative nicotine-related products such as e-cigarettes. Prenatal exposure to tobacco increases the risk of psychiatric disorders in children. Adolescence is a complex phase in which higher cognitive and emotional processes undergo maturation and refinement. In this study, we examined the behavioral and molecular effects of first-trimester prenatal exposure to e-cigarettes. Adult female mice were divided into normal air, vehicle, and 2.5%-nicotine-exposed groups. Our analyses indicated that the adolescents in the 2.5%-nicotine-exposed group exhibited a significant lack of normal digging behavior, elevated initial sucrose intake, and reduced recognition memory. Importantly, we identified a substantial level of nicotine self-administration in the 2.5%-nicotine-exposed group. At a molecular level, the mRNAs of metabotropic glutamate receptors and transporters in the nucleus accumbens were not altered. This previously undescribed work indicates that prenatal exposure to e-cigarettes might increase the risk of nicotine addiction during adolescence, reduce cognitive capacity, and alter normal adolescent behavior. The outcome will aid in translating research and assist healthcare practitioners in tackling addiction and mental issues caused by toxicological exposure. Further, it will inform relevant policymaking, such as recommended taxation, labeling e-cigarette devices with more detailed neurotoxic effects, and preventing their sale to pregnant women and adolescents.