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 ni cotine exposure by two different routes of drug administration, inject ion and infusion, on the development of monoaminergic systems and open field behavior in the neonatal and juvenile rat. The nicotine adminis tration to pregnant Sprague-Dawley rats was carried out by subcutaneou s injection (3 mg/kg twice daily) or infusion via implanted osmotic mi nipumps (6 mg/kg/day) from gestational day 4 (GD4) until GD20. At post natal day 7 (PD7), 15 and 22, the contents of the neurotransmitters an d their metabolites, including noradrenaline (NA), dopamine (DA), dihy droxyphenylacetic acid (DOPAC), homovanilic acid (HVA), serotonin (5-H T) and 5-hydroxy-3-indolacetic acid (5-HIAA) were measured in the midb rain + 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 affe cted 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 fou nd. Although there was no effect of prenatal nicotine on NE contents, the involvement of this system remains uncertain since we measured onl y NE contents without metabolites. In the present study, we also found significant route-related changes in the contents of the monoamines a nd metabolites in the NA, DA and 5-HT systems in all brain regions in rat offspring besides the effects of prenatal nicotine, In addition, t he difference in administration route reflected the results of the ope n field test and the number of ambulations in the injection-group was less than that in the infusion-groups with no relation to nicotine adm inistration. Therefore, such effects of ''prenatal stress'' accompanie d by drug administration are not negligible in considering the risk as sessment of prenatal nicotine exposure. (C) 1997 Elsevier Science B.V.