Prenatal nicotine exposure (PNE) has been associated with increased prevalence of attention deficit hyperactivity disorder (ADHD), major depressive disorder (MDD) and substance abuse in exposed children and adolescents. Whether these syndromes are caused by nicotine exposure, or genetic and psychosocial adversities associated with maternal smoking is not completely clear. Animal models suggest a direct impact of PNE. However, the fact that nicotine is forcefully administrated in these paradigms raises some questions about the specificity of these findings. Pregnant C57BI/6J mice were allowed to choose drinking saccharin/nicotine solutions or pure water. Controls could choose saccharin solutions or pure water. Offspring were tested in spontaneous locomotion, fear-associated learning (trace conditioning), addictive (conditioned place preference), and depression-like (learned helplessness) behaviors. There was no significant difference in weight or pup number between the prenatal treatment groups. A significant effect of PNE was observed on spontaneous locomotion, preference for a cocaine-associated place, and latency to escape in the learned helplessness paradigm. Surprisingly, PNE mice exhibited an increased learning of trace-conditioned fear-associated cues. The hyperlocomotive behavior reported in animal models of PNE is not likely an artifact of forceful nicotine administration. The increased prevalence of ADHD, MDD and substance abuse observed in PNE children and adolescents is probably caused by direct behavioral teratogenic effects of PNE. The role of PNE as a risk factor of syndromes associated to increased learning of fear-associated cues such as post-traumatic stress disorder (PTSD) warrants further evaluation.
PurposeThe Surgeon General's 2001 report entitled “Women and Smoking” found that between 12% (from studies of birth certificates) to 22% (according to surveys) of U.S. mothers smoked while pregnant. Many studies have demonstrated that infants prenatally exposed to nicotine show more signs of stress, hyper-excitability, and addictability, as well as oppositional, aggressive and overactive behavior. Nicotine, a predominant substance found in cigarettes, also functions as a neurotransmitter at Nicotinic Acetycholine Receptors (nAChRs). It has been demonstrated that chronic nicotine exposure in mice leads to down-regulation of existing nAChRs. Such findings suggest that Prenatal Nicotine Exposure (PNE) may affect the development of nAChR-regulated pathways, thereby producing the cognitive, emotional, and behavioral abnormalities found in offspring prenatally exposed to nicotine.MethodsDuring gestation, 12 female dams were fed a nicotine/saccharine solution, 12 other female dams were fed a nicotine/water solution, for a total of 24 dams. A power analysis was used to identify the minimum number of animals needed to avoid a Type II error. A sample size of at least 10 would provide a 90% power for significance determinations. There were three arms to the study. 1) Locomotor Activity Measurement- Quantified via Opto-varimex were the following behaviors: horizontal activity, total distance traveled, ambulatory time, rest time, vertical activity, stereotypic activity, and time spent in stereotypic activity. 2) Learned Helplessness- Mice were conditioned to associate a tone with a subsequent foot shock. In a novel, environment mice were again exposed to the tone without shock. Mice were observed for freezing behavior as a measure of learning. 3) Place Preference- Mice were conditioned with either a saline or cocaine injection in two distinct rooms and isolated in each room, respectively. Mice were later allowed free access to either room. Time spent in the drug-paired side was compared to time spent in the saline-paired side.ResultsPNE mice were shown to be more hyperactive, displayed greater learning of painful stimuli, and exhibited enhanced addictability compared to non-PNE mice.ConclusionsThe negative and numerous effects of inhaling smoke have been generally known for sometime. Our research shows that aside from the negative effects of second-hand smoke exposure, there are negative effects from second-hand nicotine exposure, as well. A greater effort must be made by proponents of public health to prevent women from smoking while pregnant.
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