Nicotine e-cigarette exposure in utero diminishes spatial memory and has negative effects on attention in a dose-, diet- and sex-dependent manner.

Rationale: Clinical and preclinical literature has linked prenatal nicotine exposure to several cognitive effects, including memory and attentional deficits. However, many preclinical studies focus on effects during adulthood and do not use clinically relevant nicotine delivery system. Objective: Our study aims to examine the impact of prenatal nicotine exposure on cognition in adolescents using an inhalation model to mimic e-cigarette exposure. Methods: Pregnant rats were exposed to either air, 24 mg/mL nicotine (low-dose nicotine, LDNIC), or 59 mg/mL nicotine (high-dose nicotine, HDNIC). Inhalations were conducted daily from 0900 to 1100. Offspring from each of the treatment groups were provided with a normal diet (ND) or high-fat diet (HFD). Novel object recognition (NOR), Morris water maze (MWM), and object-based attention (OBA) testing were conducted during early (PND 24-30) and late-adolescent (PND 44-51) periods. Results: NOR indicated that prenatal HDNIC rats spent significantly less time exploring objects compared to air controls. Altered exploratory behavior was also observed in OBA in a dose-dependent manner. HDNIC ND rats also displayed signs of memory deficit, and this was seen most robustly in HDNIC ND female rats, with no observed effects in the HFD group. Conclusions: Overall, our study indicates that prenatal vaporized nicotine exposure negatively affects spatial memory and appears to diminish performance in attention-related tasks, while HFD seems to protect from these negative effects.