Alterations of brain tissue in fetal rats exposed to nicotine in utero: possible involvement of nitric oxide and catecholamines

Histopathological changes in the brains of embryos from female rats treated with nicotine during pregnancy and possible involvement of nitric oxide (NO) and catecholamines in the nicotine-induced abnormalities of developing brain were investigated. Sexually mature female Wistar rats were given 1, 2, and 3 mg/kg nicotine hydrogen tartrate (NHT) subcutaneously for 20 days after mating. Levels of cotinine, a nicotine metabolite, in the maternal plasma increased dose-dependently. Fetus and fetal brain weights were significantly lower in all nicotine-treated groups. Light microscopy of hippocampal CA1 area showed a decrease in the number of cells per unit area. Electron microscopy of the same region revealed a dose-dependent increase in intracytoplasmic edema, mitochondrial swelling, dilation of rough endoplasmic reticulum, nuclear configurative abnormalities, and condensation of the nuclear chromatin. Nitrate+nitrite levels in fetal brain homogenates were significantly lower in the groups treated with 2 and 3 mg/kg NHT. Norepinephrine and normetanephrine (NMN) levels were significantly higher in 2 and 3 mg/kg NHT groups, as well as dopamine, 3-methoxy-4-hydroxyphenylethyleneglycole (MHPG), and dihydroxyphenylaceticacid levels in the 3-mg/kg NHT group. In conclusion, maternal nicotine exposure may lead to structural abnormalities of the fetal brain tissue and may result in decreased levels of NO and increased levels of catecholamines and their metabolites. (C) 2003 Elsevier Inc. All rights reserved.