Prenatal exposure to nicotine impairs nervous system development at a dose which does not affect viability or growth.
Prenatal exposure to high doses of nicotine (greater than 6 mg/kg/day) via maternal infusions has been shown to impair nervous system development and to decrease viability and growth. In the current study, we have examined the effects of infusing pregnant rats with 2 mg/kg of nicotine per day from gestational days 4 through 20. At this lower dose, there was neither interference with maternal weight gain nor any increase in resorption rate. Intrauterine and postnatal growth was maintained at normal or supranormal rates in the exposed offspring. Nevertheless, sufficient nicotine penetrated the fetal brain to cause persistent alterations in [3H]nicotine binding sites, abnormalities of cellular development [assessed by measurements of ornithine decarboxylase (ODC) activity and deoxyribonucleic acid (DNA)], and impairment of development of peripheral noradrenergic projections (assessed by kidney norepinephrine levels); in each case, the neural alterations were virtually equivalent to those obtained previously at the higher, growth-suppressant dosage. These findings indicate that growth impairment alone is insufficient to predict the adverse effects of nicotine on development.
Navarro
H A
HA
Department of Pharmacology, Duke University Medical Center, Durham, NC 27710.
Seidler
F J
FJ
Schwartz
R D
RD
Baker
F E
FE
Dobbins
S S
SS
Slotkin
T A
TA
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D004247:DNA / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006128:Growth / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D009538:Nicotine / Q000378:metabolism / Q000633:toxicity*; D009638:Norepinephrine / Q000378:metabolism; D065108:Ornithine Decarboxylase Inhibitors; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011919:Rats, Inbred Strains
D065108:Ornithine Decarboxylase Inhibitors; D009538:Nicotine; D004247:DNA; D009638:Norepinephrine