Effects of prenatal nicotine exposure on neuronal development: selective actions on central and peripheral catecholaminergic pathways.
The effects of prenatal nicotine exposure on development of catecholaminergic pathways were examined through measurements of transmitter turnover and levels in both the central and peripheral nervous system. Administration of nicotine (3 mg/kg SC, twice daily) to pregnant rats on gestational days 3 through 20 resulted in growth retardation which did not spare the brain and which did not resolve until after weaning. Nicotine exposure produced an elevation in transmitter turnover in central noradrenergic pathways with a regional selectivity reflecting the timetable of cellular development: the most profound effects were seen in late-developing regions (cerebellum), intermediate effects were found in earlier-developing areas (cerebral cortex) and the least effect was obtained where maturation occurs earliest (midbrain + brainstem). Dopaminergic pathways were much less vulnerable than was the noradrenergic system. Effects on the peripheral sympathetic nervous system also were targeted toward specific neuronal populations: renal, cardiac and adrenal pathways were activated by prenatal nicotine exposure, whereas sympathetic innervation of the lung showed reduced activity. All the peripheral effects appeared only after the second postnatal week. These results indicate that prenatal nicotine exposure produces profound alterations in transmitter disposition which are targeted toward specific neuronal populations and which may depend upon generalized effects on cellular development of specific brain regions. Because altered peripheral nerve activity was seen only after the onset of central control of sympathetic tone, actions on central regulation may play a role in the relatively more profound effects in the autonomic nervous system.
Slotkin, TA; Cho, H; Whitmore, WL
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