Prenatal nicotine exposure affects the development of the central serotonergic system as well as the dopaminergic system in rat offspring: involvement of route of drug administrations.

The present study was undertaken to examine the effects of prenatal nicotine exposure by two different routes of drug administration, injection and infusion, on the development of monoaminergic systems and open field behavior in the neonatal and juvenile rat. The nicotine administration to pregnant Sprague-Dawley rats was carried out by subcutaneous injection (3 mg/kg twice daily) or infusion via implanted osmotic minipumps (6 mg/kg/day) from gestational day 4 (GD4) until GD20. At postnatal day 7 (PD7), 15 and 22, the contents of the neurotransmitters and their metabolites including noradrenaline (NA), dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanilic acid (HVA), serotonin (5-HT) and 5-hydroxy-3-indolacetic acid (5-HIAA) were measured in the midbrain+pons - medulla (M + P - M), forebrain and cerebellum. Prenatal nicotine exposure caused a persistent reduction of DA turnover in the forebrain at PD15 and PD22. In addition, the 5-HT system was also affected by prenatal nicotine, and reductions of 5-HT turnover in the M + P - M at PD15 and in the forebrain and the cerebellum at PD22 were found. Although there was no effect of prenatal nicotine on NE contents, the involvement of this system remains uncertain since we measured only NE contents without metabolites. In the present study, we also found significant route-related changes in the contents of the monoamines and metabolites in the NA, DA and 5-HT systems in all brain regions in rat offspring besides the effects of prenatal nicotine. In addition, the difference in administration route reflected the results of the open field test and the number of ambulations in the injection-group was less than that in the infusion-groups with no relation to nicotine administration. Therefore, such effects of "prenatal stress" accompanied by drug administration are not negligible in considering the risk assessment of prenatal nicotine exposure.