Thesis
The Effects of Prenatal Alcohol and Nicotine Exposure on Later-Life Drug-Seeking Behavior and Memory Performance
by Fatima Iqbal
Project Overview
The study investigates the effects of prenatal exposure to alcohol and nicotine, both individually and in combination, on later-life drug-seeking behavior and memory performance using a preclinical rat model. The research used pregnant Sprague-Dawley rats and their offspring, which were divided into four prenatal exposure conditions consisting of alcohol and nicotine exposure, alcohol exposure alone, nicotine exposure alone, and a control condition. Prenatal exposure was conducted during gestational days 5–11, representing an early developmental period comparable to the first trimester in humans within the study’s model. The offspring were subsequently assessed during adolescence and adulthood to examine behavioral and cognitive outcomes. Drug-seeking behavior was evaluated through nicotine self-administration over 15 consecutive days, with measures including total nose pokes, valid nose pokes, and nicotine vapor deliveries. Memory performance was examined using the Novel Object Recognition test during both adolescence and adulthood. The findings did not demonstrate significant differences between the prenatal exposure groups in overall drug-seeking behavior. However, sex-related differences were observed, with female subjects interacting with the nose-poke hole more frequently than males, particularly among nicotine self-administering animals, and females also showing higher numbers of nicotine vapor deliveries, suggesting potentially greater nicotine-seeking behavior. Regarding memory, adolescent offspring exposed to prenatal alcohol alone demonstrated impaired performance in the Novel Object Recognition task, showing significantly greater interest in the familiar object rather than the novel object.
The prenatal nicotine-only group showed a similar pattern during adolescence, although the effect did not reach statistical significance. In adulthood, the prenatal nicotine-only group demonstrated a significantly smaller discriminatory index compared with the control group. Additional analysis indicated that adult subjects with prenatal nicotine exposure were generally more active and interacted more with both objects, which may have influenced the interpretation of the memory findings. Overall, the study did not find significant evidence that prenatal combined alcohol and nicotine exposure produced the stronger memory impairment that had been hypothesized. The study also examined developmental milestones and found that prenatal alcohol exposure was associated with delays in ear unfurling and eye opening, while combined alcohol and nicotine exposure produced an interactive effect on the timing of teeth eruption. The offspring exposed to combined substances also generally showed lower body weight during the relevant developmental period, although these findings require cautious interpretation.
Differences in food and water consumption were also observed according to sex and prenatal exposure condition. The thesis identifies several methodological limitations, including the absence of formal training for nicotine self-administration because the animals began self-administering naturally, and the lack of an acclimation period before the Novel Object Recognition task, which may have contributed to object preferences and the absence of significant overall learning effects. The findings therefore suggest that the consequences of prenatal alcohol and nicotine exposure are complex and may vary according to the substance involved, sex, developmental stage, and behavioral measure used. Overall, the research concludes that combined prenatal alcohol and nicotine exposure did not significantly increase later drug-seeking behavior or produce the expected exacerbation of memory impairment, while individual prenatal exposures, particularly alcohol and nicotine, were associated with certain developmental and cognitive differences.