An oral gastric intubation model to study the short-term and long-term effects of nicotine on body growth and brain development

Maternal smoking during pregnancy is a serious health problem associated with developmental deficits in the offspring. The third gestational trimester in human is believed to be the most important period with regard to brain development and body weight gain in the fetus, which corresponds to the first postnatal week in rodents. To evaluate the direct effects of nicotine, the major psychoactive component of tobacco, on fetal development during this critical period, we developed an oral gastric intubation model to expose neonatal rat pups to chronic nicotine. This approach resulted in blood nicotine levels closely mimicking the peak levels seen in heavy smokers and smoking mothers. We investigated the effects of nicotine on body growth, since low birth weight in the offspring is a very common consequence of maternal smoking. We also detected the effects of chronic neonatal nicotine on brain development and long-term behavioral and cognitive deficits, another possible consequence of maternal smoking. We found neonatal chronic nicotine treatment in rat pups caused reduced weight gain during the treatment period. Feeding peptide expression was upregulated by chronic nicotine in the arcuate nucleus and could be a potential mechanism of nicotine's effect on body weight. With respect to the developing brain, we found that neonatal chronic nicotine increased the nicotinic acetylcholine receptor binding sites, altered cellular morphology and decreased cell death in the hippocampus and cerebellum, two late developing brain structures. In addition, animals postnatally exposed to nicotine did not exhibit decreased learning and memory performance but exhibited an elevated anxiety level in adolescent and adult animals. The effective nicotine concentrations, reduced body weight gain, upregulated nicotinic receptor binding sites, altered apoptosis and morphology in certain brain areas indicate that the chronic nicotine exposure model is a valid approach to investigate the direct effects of nicotine. These immediate effects of nicotine on the hippocampus and cerebellum could contribute to the long-term behavioral deficits.