Changes in maternal and fetal nicotine distribution after maternal administration of monoclonal nicotine-specific antibody to rats.
Vaccination against nicotine to elicit the production of nicotine-specific antibodies is a potential treatment for tobacco addiction which reduces nicotine distribution from serum to brain. Vaccination of pregnant rats also reduces the distribution of maternally-administered nicotine to the fetal brain. Whether this is due to maternal antibody reducing the transfer of nicotine from mother to fetus, or to fetal antibody altering the distribution of nicotine within the fetus, is not clear. In the current study, passive immunization of rats with the murine monoclonal nicotine-specific antibody Nic311 was used as a surrogate for vaccination because antibody transfer to the fetus was anticipated to be lower than with vaccination. Pregnant rats received nicotine from gestational day (GD) 18-20 as frequent i.v. boluses to simulate nicotine exposure from smoking. Nic311 was administered at doses of 30, 80 or 240 mg/kg on GD 19. Fetal serum Nic311 levels on GD 20 were <3% of concurrent maternal levels, but concentrations of up to 20 ug/ml in fetal serum were obtained owing to the very high levels in maternal serum. Accumulation of the chronically administered nicotine, measured on GD 20, was not changed by Nic311 treatment in either maternal or fetal brain. The early distribution of nicotine to maternal brain, measured 5 min after a dose, was markedly reduced by Nic311, while the early distribution of nicotine to whole fetus and fetal brain was not substantially altered. These data suggest that the limited transfer of Nic311 to the fetus in turn limits the ability of Nic311 to reduce nicotine distribution to the fetal brain.
Keyler
D E
DE
College of Pharmacy, University of Minnesota Minneapolis, MN, United States; Minneapolis Medical Research Foundation, Minneapolis, MN, United States.
Lesage
M G
MG
Dufek
M B
MB
Pentel
P R
PR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D005260:Female; D007116:Immunization, Passive; D008431:Maternal-Fetal Exchange; D051379:Mice; D009538:Nicotine / Q000097:blood / Q000276:immunology* / Q000493:pharmacokinetics*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D000911:Antibodies, Monoclonal; D009538:Nicotine