Vol. 305, Issue 2, 587-592, May 2003

Maternal Vaccination Against Nicotine Reduces Nicotine Distribution to Fetal Brain in Rats

D. E. Keyler , D. Shoeman, M. G. LeSage, A. D. Calvin and P. R. Pentel

Minneapolis Medical Research Foundation (D.E.K., D.S., M.G.L., P.R.P.); Hennepin County Medical Center (D.E.K., P.R.P.); Department of Pharmacology, University of Minnesota Medical School (P.R.P.); College of Pharmacy, University of Minnesota (D.E.K.); and School of Public Health, University of Minnesota (A.D.C.) Minneapolis, Minnesota

Cigarette smoking during pregnancy is associated with a variety of adverse fetal outcomes. Nicotine is a likely contributor to these adverse effects, with fetal brain as one target organ. Vaccination of adult male rats against nicotine has been shown to reduce nicotine distribution to the brain. The current study examined whether vaccination of female rats before pregnancy would reduce the distribution to fetal brain of a single nicotine dose administered during gestation. Female rats immunized with a nicotine conjugate vaccine received a single dose of nicotine 0.03 mg/kg i.v. on gestational day 16 to 22. Five minutes later, vaccinated rats had substantially higher bound and lower unbound serum nicotine concentration and lower brain nicotine concentration than controls. Fetal brain nicotine concentration was reduced by 43% in vaccinated rats, comparable to the reduction in the maternal brain nicotine concentration. The whole-fetus nicotine concentration was not altered by vaccination. A similar experiment was performed in which pregnant rats were passively immunized with rabbit nicotine-specific IgG 7 or 21 mg/kg just before nicotine dosing. The effects of passive immunization on nicotine distribution in the mother were IgG dose-related and the higher dose reduced nicotine distribution to fetal brain by 60%. These data suggest that vaccine effects on nicotine distribution to serum and brain are similar in pregnant female rats to those previously reported in adult males. Vaccination of female rats before pregnancy, or passive immunization during pregnancy, can reduce the exposure of fetal brain to a single dose of maternally administered nicotine.