Prenatal exposure to nicotine via maternal infusions: effects on development of catecholamine systems.
The effects of a continuous 16-day gestational exposure to nicotine on development of central and peripheral catecholaminergic pathways were examined in the offspring of dams who received a minipump implant on the 4th day of gestation. Prenatal nicotine exposure resulted in a selective suppression of maturational increases in norepinephrine and dopamine levels and utilization rates in the cerebral cortex and also reduced transmitter levels in sympathetic pathways to the lung and kidney. The regional selectivity of the effect, combined with measurements of synaptosomal uptake of [3H]norepinephrine and of tyrosine hydroxylase activity, all suggested that the alterations in transmitter disposition reflected reduced neural activity as opposed to actions on general cellular development or synaptogenesis. Although the lag in development was largely made up by weaning, deficits in norepinephrine utilization reappeared in young adulthood in the cerebral cortex and midbrain + brainstem, suggesting that lasting functional alterations may occur as a consequence of prenatal nicotine exposure. Comparisons with the results obtained with maternal nicotine injections (which produce largely stimulatory effects on norepinephrine levels and turnover) suggest that the hypoxia/ischemia associated with injected nicotine causes a reactive hyperinnervation; the adverse actions of nicotine on neurotransmitter development are thus highly dependent upon the route of drug administration.
Navarro
H A
HA
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina.
Seidler
F J
FJ
Whitmore
W L
WL
Slotkin
T A
TA
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002395:Catecholamines / Q000032:analysis* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000187:drug effects*; D008431:Maternal-Fetal Exchange; D009538:Nicotine / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D013564:Sympathetic Nervous System / Q000187:drug effects*
D002395:Catecholamines; D009538:Nicotine