Reduced nicotine distribution from mother to fetal brain
in rats vaccinated against nicotine: time course and influence of nicotine
dosing regimen.
Keyler DR, Dufek MB, Calvin AD, Bramwell TJ, LeSage MG, Raphael DE,
Ross CA, Le CT, Petnel PR
Minneapolis Medical Research Foundation, Hennepin County Medical Center,
Minneapolis, MN 55415, USA.
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 <1% of
maternal serum. Although nicotine transfer to the whole fetus was not
reduced by vaccination, protein binding data suggest that nicotine-specific
antibody transferred from mother to fetus served to bind nicotine in fetal
serum, reduce the unbound nicotine concentration, and thereby reduce
nicotine distribution to fetal brain. These data comment on the safety of
vaccination against nicotine during pregnancy, and suggest that vaccination
may reduce the distribution of nicotine to fetal brain under some nicotine
dosing conditions.