Reduced nicotine distribution from mother to fetal brain in rats vaccinated against nicotine: Time course and influence of nicotine dosing regimen

Nicotine is a teratogen in rats and possibly in humans. Vaccination against nicotine is being studied as a possible treatment for nicotine dependence. The safety of maternal vaccination against nicotine during or prior to pregnancy is not known. In this study, female rats were vaccinated and then ad...

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Bibliographic Details
Published in:Biochemical pharmacology 2005-05, Vol.69 (9), p.1385-1395
Main Authors: Keyler, Daniel E., Dufek, Matthew B., Calvin, Andrew D., Bramwell, Thomas J., LeSage, Mark G., Raphael, Donna E., Ross, Cathy A., Le, Chap T., Pentel, Paul R.
Format: Article
Language:English
Subjects:
Animals
Antibody
Biological and medical sciences
Brain - drug effects
Brain - metabolism
Enzyme-Linked Immunosorbent Assay
Female
Fetal
Fetus
Maternal-Fetal Exchange
Medical sciences
Nicotine
Nicotine - immunology
Nicotine - pharmacokinetics
Nicotinic Agonists - immunology
Nicotinic Agonists - pharmacology
Pharmacokinetics
Pharmacology. Drug treatments
Pregnancy
Protein Binding
Rats
Rats, Sprague-Dawley
Time Factors
Tissue Distribution
Vaccination
Vaccine
Vaccines, Conjugate - administration & dosage
Vaccines, Conjugate - immunology
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Summary:Nicotine is a teratogen in rats and possibly in humans. Vaccination against nicotine is being studied as a possible treatment for nicotine dependence. The safety of maternal vaccination against nicotine during or prior to pregnancy is not known. In this study, female rats were vaccinated and then administered acute or chronic nicotine during pregnancy at doses simulating nicotine exposure in smokers. Maternal vaccination reduced nicotine distribution to both maternal brain (44–47%) and fetal brain (17–39%) for up to 25 min after a single maternal nicotine dose administered on gestational day (GD) 20, but had a smaller effect on nicotine distribution to brain after continuous nicotine infusion. Nicotine distribution to maternal or fetal brain after repeated nicotine bolus doses was reduced immediately following an individual dose in vaccinated rats, but the chronic accumulation of nicotine in fetal brain was not altered. Nicotine distribution to whole fetus, in contrast to fetal brain, was generally not altered by vaccination. Nicotine-specific antibody concentration in fetal serum was 10% that of maternal serum, and in fetal brain was
ISSN:0006-2952
1873-2968
DOI:10.1016/j.bcp.2005.02.007