Effects of prenatal nicotine exposure on development of central and peripheral cholinergic neurotransmitter systems. Evidence for cholinergic trophic influences in developing brain.
The development of cholinergic systems in brain regions was evaluated biochemically in developing control rats and rats whose mothers received nicotine via continuous minipump infusion during gestational days 4 to 20. The cerebral cortex displayed a unique maturational pattern of choline acetyltransferase (ChAT) activity and high-affinity synaptosomal [3H]choline uptake capabilities, characterized by increases in the concentration of these components and a postnatal spike of neuronal activity as assessed with the uptake/ChAT ratio; the peak of activity coincided with the time at which neurogenesis declines and synaptogenesis rises. Evaluation of the same markers in midbrain + brainstem indicated rises in uptake which were relatively unselective, primarily reflecting tissue growth and no postnatal peak of uptake/ChAT; cerebellum likewise showed primarily tissue growth-related changes in ChAT rather than increases in its specific concentration. Prenatal exposure to nicotine had a marked adverse effect on developmental patterns of ChAT, uptake and uptake/ChAT only in cerebral cortex, the region previously shown to exhibit major abnormalities caused by this drug and other treatments with cholinomimetic effects. ChAT was unaffected in peripheral projections to the adrenal. Nicotine may thus selectively disrupt central nervous system development by stimulating nicotinic receptors which are present in fetal brain, prematurely eliciting the events ordinarily triggered postnatally by cholinergic projections.
Navarro
H A
HA
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina.
Seidler
F J
FJ
Eylers
J P
JP
Baker
F E
FE
Dobbins
S S
SS
Lappi
S E
SE
Slotkin
T A
TA
D000818:Animals; D001921:Brain / Q000187:drug effects*; D002794:Choline / Q000493:pharmacokinetics; D002795:Choline O-Acetyltransferase / Q000032:analysis; D005260:Female; D005333:Fetus / Q000187:drug effects*; D006128:Growth / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology*; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains
D009538:Nicotine; D002795:Choline O-Acetyltransferase; D002794:Choline