Effects of Pre- and Neonatal Nicotine Exposure in Rodents: Inconsistent Evidence

Abstract

This review presents an analysis of the literature on behavioral effects of developmental exposure to nicotine, as assessed in rodent models that mimic the consequences for human offspring of maternal cigarette smoking. Despite the frequency of reports of low birth weight, hyperactivity, cognitive deficits, and psychiatric problems, inconsistencies exist in both the clinical and experimental literature. Confounding socioeconomic and other demographic variables may account for discrepancies in clinical reports, and the choice of developmental exposure period and the method of nicotine administration may explain differences in experimental outcomes. Analysis of a number of variables (e.g., physical, behavioral, and cognitive) shows that fetal exposure to nicotine does not consistently cause growth retardation or decreased birth weight, nor reliably affect motor activity. But combined pre- and neonatal exposure is likely to result in delayed reflex development, global impairments in learning and memory, and an increased incidence of symptoms that model psychiatric illness. There is also support for increased self-administration of nicotine and other drugs of abuse in animals exposed developmentally to nicotine, as well as potent effects on offspring responses to drug challenges. Unlike reports in the clinical literature, sexually dimorphic effects were not evident in most animal models. Possible neuroanatomical and cholinergic mechanisms responsible for behavioral changes are briefly discussed. Statistical and design considerations are provided to increase the translational value of this research and, most importantly, enhance the replicability of reported findings.

Developmental toxicity of nicotine: A transdisciplinary synthesis and implications for emerging tobacco products

“…(180) Activity levels have also been studied using rodent models, again with inconsistent results, perhaps reflecting differences in the developmental exposure period and the method of nicotine administration, or, in some cases, lack of sufficient statistical power in the experimental design. (180) In contrast, there is greater consistency among animal studies examining the effects of prenatal nicotine exposure on cognitive development, suggestive of global impairments in learning and memory. (181)(182)(183)(184)(185)(186)(187)(188)(189)(190) These effects appear to be dose dependent and sensitive to factors such as sex and timing of exposure.…”